Gregory Hammer

All Publications

• A multicenter study to evaluate the pharmacokinetics and safety of liposomal bupivacaine for postsurgical analgesia in pediatric patients aged 6 to less than 17years (PLAY). Journal of clinical anesthesia Tirotta, C. F., de Armendi, A. J., Horn, N. D., Hammer, G. B., Szczodry, M., Matuszczak, M., Wang, N. Q., Scranton, R., Ballock, R. T. 2021; 75: 110503

  Abstract

  STUDY OBJECTIVE: To evaluate the pharmacokinetics and safety of liposomal bupivacaine in pediatric patients undergoing spine or cardiac surgery.DESIGN: Multicenter, open-label, phase 3, randomized trial (PLAY; NCT03682302).SETTING: Operating room.PATIENTS: Two separate age groups were evaluated (age group 1: patients 12 to <17years undergoing spine surgery; age group 2: patients 6 to <12years undergoing spine or cardiac surgery).INTERVENTION: Randomized allocation of liposomal bupivacaine 4mg/kg or bupivacaine hydrochloride (HCl) 2mg/kg via local infiltration at the end of spine surgery (age group 1); liposomal bupivacaine 4mg/kg via local infiltration at the end of spine or cardiac surgery (age group 2).MEASUREMENTS: The primary and secondary objectives were to evaluate the pharmacokinetics (eg, maximum plasma bupivacaine concentrations [Cmax], time to Cmax) and safety of liposomal bupivacaine, respectively.MAIN RESULTS: Baseline characteristics were comparable across groups. Mean Cmax after liposomal bupivacaine administration was lower versus bupivacaine HCl in age group 1 (357 vs 564ng/mL); mean Cmax in age group 2 was 320 and 447ng/mL for spine and cardiac surgery, respectively. Median time to Cmax of liposomal bupivacaine occurred later with cardiac surgery versus spine surgery (22.7 vs 7.4h). In age group 1, the incidence of adverse events (AEs) was comparable between liposomal bupivacaine (61% [19/31]) and bupivacaine HCl (73% [22/30]). In age group 2, 100% (5/5) and 31% (9/29) of patients undergoing spine and cardiac surgery experienced AEs, respectively. AEs were generally mild or moderate, with no discontinuations due to AEs or deaths.CONCLUSIONS: Plasma bupivacaine levels following local infiltration with liposomal bupivacaine remained below the toxic threshold in adults (~2000-4000ng/mL) across age groups and procedures. AEs were mild to moderate, supporting the safety of liposomal bupivacaine in pediatric patients undergoing spine or cardiac surgery. Clinical trial number and registry URL: ClinicalTrials.gov identifier: NCT03682302.

  View details for DOI 10.1016/j.jclinane.2021.110503

  View details for PubMedID 34534923

• Oliceridine Exhibits Improved Tolerability Compared to Morphine at Equianalgesic Conditions: Exploratory Analysis from Two Phase 3 Randomized Placebo and Active Controlled Trials. Pain and therapy Hammer, G. B., Khanna, A. K., Michalsky, C., Wase, L., Demitrack, M. A., Little, R., Fossler, M. J., Ayad, S. 2021

  Abstract

  INTRODUCTION: In the management of postoperative acute moderate-to-severe pain, opioids remain an important component. However, conventional opioids have a narrow therapeutic index and are associated with dose-limiting opioid-related adverse events (ORAEs) that can result in worse patient outcomes. Oliceridine, a new intravenous -opioid receptor agonist, is shown in nonclinical studies to be biased for G protein signaling (achieving analgesia) with limited recruitment of beta-arrestin (associated with ORAEs). In two phase 3 randomized controlled studies of patients with moderate-to-severe acute pain following hard or soft tissue surgery, in which analgesia was measured using Sum of Pain Intensity Differences (SPID) from baseline over 48 and 24h (SPID-48 and -24 respectively, oliceridine at demand doses of 0.1, 0.35, or 0.5mg was highly effective compared to placebo, with a favorable safety profile compared to morphine. This exploratory analysis was conducted to determine whether the safety benefits seen with oliceridine persisted when adjusted for equal levels of analgesia compared to morphine.METHODS: Presence of at least one treatment-emergent ORAE (based on Medical Dictionary for Regulatory Activities [MedDRA]-coded events: hypoxemia, nausea, vomiting, sedation, pruritus, or dizziness) was used as the composite safety endpoint. A logistic regression model was utilized to compare oliceridine (pooled regimens) versus morphine, after controlling for analgesia (using SPID-48 or SPID-24 with pre-rescue scores carried forward 6h). This analysis excluded patients receiving placebo and was repeated for each study and for pooled data.RESULTS: At a given level of SPID-48 or SPID-24, patients receiving oliceridine were less likely to experience the composite safety endpoint. Although not statistically significant at the 0.05 level in the soft tissue model, the odds ratio (OR) showed a consistent numerical trend for oliceridine, being approximately half that observed with morphine in both the hard (OR 0.499; 95% confidence interval [CI] 0.255, 0.976; p=0.042) and soft (OR 0.542; 95% CI 0.250, 1.175; p=0.121) tissue studies. Results from the pooled data were consistent with those observed in the individual studies (OR 0.507; 95% CI 0.304, 0.844; p=0.009).CONCLUSION: Findings from this exploratory analysis suggest that at comparable levels of analgesia, patients receiving oliceridine were less likely to experience the composite safety endpoint consisting of ORAEs compared to patients treated with morphine.

  View details for DOI 10.1007/s40122-021-00299-0

  View details for PubMedID 34351590

• Opioid-Free Recovery After Hernia Repair with HTX-011 as the Foundation of a Non-Opioid, Multimodal Analgesia Regimen in a Real-World Setting: A Randomized, Open-Label Study. Pain and therapy Minkowitz, H., Soto, R., Fanikos, J., Hammer, G. B., Mehta, N., Hu, J., Redan, J. 2021

  Abstract

  INTRODUCTION: Helping Opioid Prescription Elimination (HOPE) is a project designed to provide surgeons with practical, real-world solutions to effectively manage postoperative pain and eliminate the need for opioids using HTX-011 (extended-release bupivacaine/low-dose meloxicam). In phase 3 herniorrhaphy and bunionectomy studies, HTX-011 without multimodal analgesia (MMA) was superior to bupivacaine hydrochloride in reducing pain and opioid consumption. Here, we examine the HOPE Hernia-1 study, which was designed to compare alternating ibuprofen/acetaminophen with concurrent use as part of an HTX-011-based non-opioid MMA regimen in patients undergoing herniorrhaphy and to evaluate the effectiveness of a personalized opioid prescription algorithm.METHODS: Patients undergoing outpatient open inguinal herniorrhaphy with intraoperative administration of HTX-011 (300mg bupivacaine/9mg meloxicam) were randomly assigned to receive a scheduled oral regimen of ibuprofen plus acetaminophen, either taken together every 6hours or alternating every 3hours, for 5days following surgery, while awake. Based on the opioid prescription algorithm evaluated here, patients could receive an oxycodone prescription upon discharge only if they had a numeric rating scale pain score of≥6 at discharge and/or had received a postoperative rescue opioid.RESULTS: The majority of patients did not require an opioid prescription through 2weeks following surgery, and this was similar between cohorts (alternating MMA, 89.1%; concurrent MMA, 93.6%). Patient satisfaction was high for both regimens, and 95% of patients had an opioid-free recovery. No patient discharged without a prescription called back to request one. Treatment was well tolerated, without evidence of nonsteroidal anti-inflammatory drug-related toxicity.CONCLUSIONS: HTX-011, used with over-the-counter products ibuprofen/acetaminophen and personalized opioid prescription algorithm in a real-world environment, has the potential to reduce opioid use and opioid prescriptions after herniorrhaphy without compromising patient satisfaction.TRIAL REGISTRATION: ClinicalTrials.gov, NCT03237481.

  View details for DOI 10.1007/s40122-021-00289-2

  View details for PubMedID 34318438

• Modeling human adaptive immune responses with tonsil organoids. Nature medicine Wagar, L. E., Salahudeen, A. n., Constantz, C. M., Wendel, B. S., Lyons, M. M., Mallajosyula, V. n., Jatt, L. P., Adamska, J. Z., Blum, L. K., Gupta, N. n., Jackson, K. J., Yang, F. n., Röltgen, K. n., Roskin, K. M., Blaine, K. M., Meister, K. D., Ahmad, I. N., Cortese, M. n., Dora, E. G., Tucker, S. N., Sperling, A. I., Jain, A. n., Davies, D. H., Felgner, P. L., Hammer, G. B., Kim, P. S., Robinson, W. H., Boyd, S. D., Kuo, C. J., Davis, M. M. 2021

  Abstract

  Most of what we know about adaptive immunity has come from inbred mouse studies, using methods that are often difficult or impossible to confirm in humans. In addition, vaccine responses in mice are often poorly predictive of responses to those same vaccines in humans. Here we use human tonsils, readily available lymphoid organs, to develop a functional organotypic system that recapitulates key germinal center features in vitro, including the production of antigen-specific antibodies, somatic hypermutation and affinity maturation, plasmablast differentiation and class-switch recombination. We use this system to define the essential cellular components necessary to produce an influenza vaccine response. We also show that it can be used to evaluate humoral immune responses to two priming antigens, rabies vaccine and an adenovirus-based severe acute respiratory syndrome coronavirus 2 vaccine, and to assess the effects of different adjuvants. This system should prove useful for studying critical mechanisms underlying adaptive immunity in much greater depth than previously possible and to rapidly test vaccine candidates and adjuvants in an entirely human system.

  View details for DOI 10.1038/s41591-020-01145-0

  View details for PubMedID 33432170

• Tapentadol for the Treatment of Moderate-to-Severe Acute Pain in Children Under the Age of Two Years. Journal of pain research Eissa, A., Tarau, E., Beuter, C., Radic, T., Watson, E., Sohns, M., Lefeber, C., Hammer, G. B. 2021; 14: 229–48

  Abstract

  Background: Pharmacokinetics (PK), efficacy, and safety of the opioid analgesic tapentadol in the treatment of moderate-to-severe acute pain have so far not been investigated in pediatric patients <2 years of age.Patients and Methods: Two multicenter, open-label trials assessed the pharmacokinetic profile, safety, tolerability, and efficacy of single doses of tapentadol oral solution (OS; NCT02221674; n=19) or intravenous infusion (IV, EudraCT 2014-002259-24; n=38) in children from birth to <2 years of age. Of these, 8 preterm neonates were included in the IV trial. A third randomized, double-blind, placebo-controlled trial (NCT02081391) investigated the efficacy and safety of multiple tapentadol OS doses in patients from birth to <2 years (placebo n=4, tapentadol n=11) using an immediate rescue trial design. Patients in all three trials underwent surgery that, in the investigator's opinion, reliably produced moderate-to-severe pain requiring opioid treatment.Results: Administration of single tapentadol doses resulted in tapentadol serum concentrations within the targeted range known to be safe and efficacious in adults and compared well to the range observed for children aged 2 to <18 years. Pain intensity already improved 15 min after administration. In the multiple dose trial, amounts of supplemental opioid analgesic medication within the first 24 h after start of trial medication were low (placebo 0.02 mg/kg, tapentadol 0.05 mg/kg). All patients stopped treatment with the trial medication because opioid analgesics were no longer required. Treatment-emergent adverse events occurred in 42.1% (tapentadol OS single dose), 28.9% (tapentadol IV), and 75% of placebo and 54.5% of tapentadol patients (tapentadol OS multiple doses), none of them serious.Conclusion: Tapentadol showed a favorable PK and safety profile in children <2 years of age. Multiple tapentadol OS dosing is efficacious and generally well tolerated in children ≥2 years and might also be a useful treatment option for children <2 years in need of strong analgesics.

  View details for DOI 10.2147/JPR.S269530

  View details for PubMedID 33542653

• Low Incidence of Opioid-Induced Respiratory Depression Observed with Oliceridine Regardless of Age or Body Mass Index: Exploratory Analysis from a Phase 3 Open-Label Trial in Postsurgical Pain. Pain and therapy Brzezinski, M. n., Hammer, G. B., Candiotti, K. A., Bergese, S. D., Pan, P. H., Bourne, M. H., Michalsky, C. n., Wase, L. n., Demitrack, M. A., Habib, A. S. 2021

  Abstract

  Advanced age and obesity are reported to increase the risk of opioid-induced respiratory depression (OIRD). Oliceridine, an intravenous opioid, is a G-protein-biased agonist at the µ-opioid receptor that may provide improved safety. The recent phase 3 ATHENA open-label, multicenter study evaluated postoperative use of oliceridine in patients with moderate-to-severe acute pain. This exploratory analysis of the ATHENA data examined the incidence of OIRD in older (≥ 65 years) and/or obese (BMI ≥ 30 kg/m2) patients and analyzed risk factors of OIRD.Patients aged ≥ 18 years with a score ≥ 4 on an 11-point numeric pain rating scale (NPRS) received IV oliceridine as needed via bolus dosing and/or patient-controlled analgesia (PCA). OIRD occurring within 48 h of last dose of oliceridine was defined using two established definitions: (1) naloxone use, (2) respiratory rate < 10 breaths per minute and/or oxygen saturation < 90%.A total of 724 surgical patients with a mean age of 54.5 ± 15.9 years and a mean NRS score of 6.2 ± 2.1 were included in this analysis; 33.3% (241/724) were ≥ 65 years of age and 46.3% (335/724) had BMI (body mass index) ≥ 30 kg/m2. The overall OIRD incidence was 13.7% with no patients requiring naloxone. The OIRD incidence was similar in the elderly and younger adults' cohorts [10.8 vs. 15.1%, OR 0.68 (0.42, 1.1), p = 0.11], and in obese and non-obese groups [14.0 vs. 13.4%, OR 1.06 (0.69, 1.62), p = 0.80]. In patients that were both elderly and obese (n = 120), the incidence was 10.8%. The multivariate analysis identified baseline NRS ≥ 6 [OR 1.6 (1.0, 2.4), p = 0.0499], PCA administration [OR 1.9 (1.2, 3.1), p = 0.005], and concomitant use of benzodiazepines and/or gabapentinoids [OR 1.6 (1.0, 2.6), p = 0.045], as being associated with OIRD.Postoperative oliceridine use in patients with advanced age and/or increased BMI was not associated with increased risk of OIRD.

  View details for DOI 10.1007/s40122-020-00232-x

  View details for PubMedID 33502739

• Mindfulness and GAIN: The Solution To Burnout in Medicine? Paediatric anaesthesia Hammer, G. B. 2020

  Abstract

  Burnout is a state of emotional and physical exhaustion associated with internal and external stressors. Drivers of burnout include the expectation that we as physicians place our patients first, ahead of our own self-care; that seeking help is a sign of weakness in the culture of medicine; practice inefficiencies, including those imposed by electronic medical records; and a lack of personal resilience suffered by many physicians. The costs of burnout are high, including a decrement in the quality of care, increased turnover, and physician suicide. Changes in the culture of medicine and practice efficiency will rely on excellent leadership. On the other hand, we are individually responsible for our personal resilience. We can enhance our resilience with a variety of tools, including meditation and mindfulness practice. Fortunately, these practices are becoming more mainstream and readily available to us. This article will briefly review the problem of burnout, including drivers and costs, and then focus on meditation and mindfulness practices that we may embrace in order to become more resilient.

  View details for DOI 10.1111/pan.14033

  View details for PubMedID 33034156

• Pharmacokinetics of Dexmedetomidine in Infants and Children After Orthotopic Liver Transplantation ANESTHESIA AND ANALGESIA Damian, M. A., Hammer, G. B., Elkomy, M. H., Frymoyer, A., Drover, D. R., Su, F. 2020; 130 (1): 209–16

  View details for DOI 10.1213/ANE.0000000000003761

  View details for Web of Science ID 000502991500038

• REDUCING OFF-LABEL DORNASE ALFA UTILIZATION THROUGH COMPUTERIZED ORDER ENTRY OPTIMIZATION Moss, J., Gaskari, S., Cornfield, D., Hammer, G. LIPPINCOTT WILLIAMS & WILKINS. 2020

  View details for Web of Science ID 000530000201673

• ATHENA: A Phase 3, Open-Label Study Of The Safety And Effectiveness Of Oliceridine (TRV130), A G-Protein Selective Agonist At The µ-Opioid Receptor, In Patients With Moderate To Severe Acute Pain Requiring Parenteral Opioid Therapy. Journal of pain research Bergese, S. D., Brzezinski, M., Hammer, G. B., Beard, T. L., Pan, P. H., Mace, S. E., Berkowitz, R. D., Cochrane, K., Wase, L., Minkowitz, H. S., Habib, A. S. 2019; 12: 3113-3126

  Abstract

  Pain management with conventional opioids can be challenging due to dose-limiting adverse events (AEs), some of which may be related to the simultaneous activation of β-arrestin (a signaling pathway associated with opioid-related AEs) and G-protein pathways. The investigational analgesic oliceridine is a G-protein-selective agonist at the µ-opioid receptor with less recruitment of β-arrestin. The objective of this phase 3, open-label, multi-center study was to evaluate the safety and tolerability, of IV oliceridine for moderate to severe acute pain in a broad, real-world patient population, including postoperative surgical patients and non-surgical patients with painful medical conditions.Adult patients with a score ≥4 on 11-point NRS for pain intensity received IV oliceridine either by bolus or PCA; multimodal analgesia was permitted. Safety was assessed using AE reports, study discontinuations, clinical laboratory and vital sign measures.A total of 768 patients received oliceridine. The mean age (SD) was 54.1 (16.1) years, with 32% ≥65 years of age. Most patients were female (65%) and Caucasian (78%). Surgical patients comprised the majority of the study population (94%), most common being orthopedic (30%), colorectal (15%) or gynecologic (15%) procedures. Multimodal analgesia was administered to 84% of patients. Oliceridine provided a rapid reduction in NRS pain score by 2.2 ± 2.3 at 30 mins from a score of 6.3 ± 2.1 (at baseline) which was maintained to the end of treatment. No deaths or significant cardiorespiratory events were reported. The incidence of AEs leading to early discontinuation and serious AEs were 2% and 3%, respectively. Nausea (31%), constipation (11%), and vomiting (10%) were the most common AEs. AEs were mostly of mild (37%) or moderate (25%) severity and considered possibly or probably related to oliceridine in 33% of patients.Oliceridine IV for the management of moderate to severe acute pain was generally safe and well tolerated in the patients studied.NCT02656875.

  View details for DOI 10.2147/JPR.S217563

  View details for PubMedID 31814753

  View details for PubMedCentralID PMC6861532

• Randomized Population Pharmacokinetic Analysis and Safety of Intravenous Acetaminophen for Acute Postoperative Pain in Neonates and Infants. Journal of clinical pharmacology Hammer, G. B., Maxwell, L. G., Taicher, B. M., Visoiu, M., Cooper, D. S., Szmuk, P., Pheng, L. H., Gosselin, N. H., Lu, J., Devarakonda, K. 2019

  Abstract

  Intravenous administration of acetaminophen is an alternative to the oral and rectal routes, which may be contraindicated in particular clinical settings. This randomized, placebo-controlled study of intravenous acetaminophen (Ofirmev, Mallinckrodt Pharmaceuticals, Bedminster, New Jersey) in neonate and infant patients with acute postoperative pain assessed pharmacokinetics (PK) and safety, in addition to efficacy and pharmacodynamics of repeated doses administered over 24hours. Neonate and infant patients (<2years of age) who were undergoing surgery or had experienced a traumatic injury and were expected to need pain management for at least 24hours were enrolled. Subjects were randomly assigned to receive intravenous acetaminophen low dose, intravenous acetaminophen high dose, or placebo. A population PK model of intravenous acetaminophen was updated by combining 581samples from the current study of 158 neonate and infant subjects with results from a previously developed model. The individual predicted-versus-observed concentrations plots showed that the structural PK model fit the blood and plasma acetaminophen concentration-versus-time profiles in the active and placebo groups. Terminal elimination half-life was prolonged in neonates and younger infants and in intermediate and older infants similar to values in adults. When compared with placebo, total rescue opioid consumption was similar and significantly fewer intravenous acetaminophen patients prematurely discontinued because of treatment-emergent adverse events (P<.01). For intravenous acetaminophen, neonates receiving 12.5mg/kg every 6hours had PK profiles similar to younger, intermediate, and older infants, adolescents, and adults weighing <50kg receiving 15mg/kg every 6hours and adults ≥ 50kg receiving 1000mg every 6hours.

  View details for DOI 10.1002/jcph.1508

  View details for PubMedID 31448420

• Antimicrobial Disposition During Pediatric Continuous Renal Replacement Therapy Using an Ex Vivo Model. Critical care medicine Purohit, P. J., Elkomy, M. H., Frymoyer, A., Sutherland, S. M., Drover, D. R., Hammer, G. B., Su, F. 2019

  Abstract

  OBJECTIVES: Little is known on the impact of continuous renal replacement therapy on antimicrobial dose requirements in children. In this study, we evaluated the pharmacokinetics of commonly administered antimicrobials in an ex vivo continuous renal replacement therapy model.DESIGN: An ex vivo continuous renal replacement therapy circuit was used to evaluate drug-circuit interactions and determine the disposition of five commonly used antimicrobials (meropenem, piperacillin, liposomal amphotericin B, caspofungin, and voriconazole).SETTING: University research laboratory.PATIENTS: None.INTERVENTIONS: Antimicrobials were administered into a reservoir containing whole human blood. The reservoir was connected to a pediatric continuous renal replacement therapy circuit programmed for a 10 kg child. Continuous renal replacement therapy was performed in the hemodiafiltration mode and in three phases correlating with three different continuous renal replacement therapy clearance rates: 1) no clearance (0 mL/kg/hr, to measure adsorption), 2) low clearance (20 mL/kg/hr), and 3) high clearance (40 mL/kg/hr). Blood samples were drawn directly from the reservoir at baseline and at 5, 20, 60, and 180 minutes during each phase. Five independent continuous renal replacement therapy runs were performed to assess inter-run variability. Antimicrobial concentrations were measured using validated liquid chromatography-mass spectrometry assays. A closed-loop, flow-through pharmacokinetic model was developed to analyze concentration-time profiles for each drug.MEASUREMENTS AND MAIN RESULTS: Circuit adsorption of antimicrobials ranged between 13% and 27%. Meropenem, piperacillin, and voriconazole were cleared by the continuous renal replacement therapy circuit and clearance increased with increasing continuous renal replacement therapy clearance rates (7.66 mL/min, 4.97 mL/min, and 2.67 mL/min, respectively, for high continuous renal replacement therapy clearance). Amphotericin B and caspofungin had minimal circuit clearance and did not change with increasing continuous renal replacement therapy clearance rates.CONCLUSIONS: Careful consideration of drug-circuit interactions during continuous renal replacement therapy is essential for appropriate drug dosing in critically ill children. Antimicrobials have unique adsorption and clearance profiles during continuous renal replacement therapy, and this knowledge is important to optimize antimicrobial therapy.

  View details for DOI 10.1097/CCM.0000000000003895

  View details for PubMedID 31306179

• ATHENA: A Phase 3, Open-Label Study Of The Safety And Effectiveness Of Oliceridine (TRV130), A G-Protein Selective Agonist At The mu-Opioid Receptor, In Patients With Moderate To Severe Acute Pain Requiring Parenteral Opioid Therapy JOURNAL OF PAIN RESEARCH Bergese, S. D., Brzezinski, M., Hammer, G. B., Beard, T. L., Pan, P. H., Mace, S. E., Berkowitz, R. D., Cochrane, K., Wase, L., Minkowitz, H. S., Habib, A. S. 2019; 12: 3113–26

  View details for DOI 10.2147/JPR.S217563

  View details for Web of Science ID 000496416700001

• Playing with dexmedetomidine pharmacokinetics! British journal of anaesthesia Hammer, G. n., Shafer, S. L. 2019

  View details for DOI 10.1016/j.bja.2019.11.019

  View details for PubMedID 31879025

• Pharmacokinetics of Dexmedetomidine in Infants and Children After Orthotopic Liver Transplantation. Anesthesia and analgesia Damian, M. A., Hammer, G. B., Elkomy, M. H., Frymoyer, A., Drover, D. R., Su, F. 2018

  Abstract

  BACKGROUND: Dexmedetomidine (DEX) is a sedative and analgesic medication that is frequently used postoperatively in children after liver transplantation. Hepatic dysfunction, including alterations in drug clearance, is common immediately after liver transplantation. However, the pharmacokinetics (PK) of DEX in this population is unknown. The objective of this study was to determine the PK profile of DEX in children after liver transplantation.METHODS: This was a single-center, open-label PK study of DEX administered as an intravenous loading dose of 0.5 mug/kg followed by a continuous infusion of 0.5 mug/kg/h. Twenty subjects, 1 month to 18 years of age, who were admitted to the pediatric intensive care unit after liver transplantation were enrolled. Whole blood was collected and analyzed for DEX concentration using a dried blood spot method. Nonlinear mixed-effects modeling was used to characterize the population PK of DEX.RESULTS: DEX PK was best described by a 2-compartment model with first-order elimination. A typical child after liver transplantation with an international normalized ratio (INR) of 1.8 was found to have a whole blood DEX clearance of 52 L/h (95% confidence interval [CI], 31-73 L/h). In addition, intercompartmental clearance was 246 L/h (95% CI, 139-391 L/h), central volume of distribution was 186 L/70 kg (95% CI, 140-301 L/70 kg), and peripheral volume of distribution was 203 L (95% CI, 123-338 L). Interindividual variability ranged from 11% to 111% for all parameters. Clearance was not found to be associated with weight but was found to be inversely proportional to INR. An increase in INR to 3.2 resulted in a 50% decrease in DEX clearance. Weight was linearly correlated with central volume of distribution. All other covariates, including age, ischemic time, total bilirubin, and alanine aminotransferase, were not found to be significant predictors of DEX disposition.CONCLUSIONS: Children who received DEX after liver transplantation have large variability in clearance, which was not found to be associated with weight but is influenced by underlying liver function, as reflected by INR. In this population, titration of DEX dosing to clinical effect may be important because weight-based dosing is poorly associated with blood concentrations. More attention to quality of DEX sedation may be warranted when INR values are changing.

  View details for PubMedID 30198929

• Unusual Catheter Placement on Chest Radiograph: Two Dimensions, Two Possible Locations (or More) ANESTHESIOLOGY Schalkwyk, A., Hammer, G. B. 2018; 128 (2): 424

  View details for PubMedID 29337757

• Phase IV, Open-Label, Safety Study Evaluating the Use of Dexmedetomidine in Pediatric Patients Undergoing Procedure-Type Sedation FRONTIERS IN PHARMACOLOGY Jooste, E. H., Hammer, G. B., Reyes, C. R., Katkade, V., Szmuk, P. 2017; 8: 529

  Abstract

  Dexmedetomidine (Precedex™) may be used as an alternative sedative in children, maintaining spontaneous breathing, and avoiding tracheal intubation in a non-intubated moderate or deep sedation (NI-MDS) approach. This open-label, single-arm, multicenter study evaluated the safety of dexmedetomidine in a pediatric population receiving NI-MDS in an operating room or a procedure room, with an intensivist or anesthesiologist in attendance, for elective diagnostic or therapeutic procedures expected to take at least 30 min. The primary endpoint was incidence of treatment-emergent adverse events (TEAEs). Patients received one of two doses dependent on age: patients aged ≥28 weeks' gestational age to <1 month postnatal received dose level 1 (0.1 μg/kg load; 0.05-0.2 μg/kg/h infusion); those aged 1 month to <17 years received dose level 2 (1 μg/kg load; 0.2-2.0 μg/kg/h infusion). Sedation efficacy was assessed and defined as adequate sedation for at least 80% of the time and successful completion of the procedure without the need for rescue medication. In all, 91 patients were enrolled (dose level 1, n = 1; dose level 2, n = 90); of these, 90 received treatment and 82 completed the study. Eight patients in dose level 2 discontinued treatment for the following reasons: early completion of diagnostic or therapeutic procedure (n = 3); change in medical condition (need for intubation) requiring deeper level of sedation (n = 2); adverse event (AE; hives and emesis), lack of efficacy, and physician decision (patient not sedated enough to complete procedure; n = 1 each). Sixty-seven patients experienced 147 TEAEs. The two most commonly reported AEs were respiratory depression (bradypnea; reported per protocol-defined criteria, based on absolute respiratory rate values for age or relative decrease of 30% from baseline) and hypotension. Four patients received glycopyrrolate for bradycardia and seven patients received intravenous fluids for hypotension. SpO2 dropped by 10% in two patients, but resolved without need for manual ventilation. All other reported AEs were consistent with the known safety profile of dexmedetomidine. Two of the 78 patients in the efficacy-evaluable population met all sedation efficacy criteria. Dexmedetomidine was well-tolerated in pediatric patients undergoing procedure-type sedation.

  View details for PubMedID 28848443

• Subglottic Stenosis Following Cardiac Surgery With Cardiopulmonary Bypass in Infants and Children. Pediatric critical care medicine Kruse, K. E., Purohit, P. J., Cadman, C. R., Su, F., Aghaeepour, N., Hammer, G. B. 2017; 18 (5): 429-433

  Abstract

  To determine the 1) incidence of subglottic stenosis in infants and children following cardiac surgery with cardiopulmonary bypass and 2) risk factors associated with its development.Retrospective cohort study.Tertiary children's hospital in California.Infants and children who underwent cardiac surgery with cardiopulmonary bypass.Diagnosis of subglottic stenosis by tracheoscopy.The incidence of subglottic stenosis at our institution during the study period was 0.7%. Young age (p = 0.014), prolonged cardiopulmonary bypass (p = 0.03), and prolonged mechanical ventilation (p < 0.01) were associated with the development of subglottic stenosis. Gender, chromosomal anomaly, presence of a cuffed endotracheal tube, and lowest core temperature during cardiopulmonary bypass were not associated with the development of subglottic stenosis.The incidence of subglottic stenosis was less than that previously reported in this population. Although the incidence is relatively low, subglottic stenosis is a serious complication of tracheal intubation and all measures to prevent subglottic stenosis should be undertaken.

  View details for DOI 10.1097/PCC.0000000000001125

  View details for PubMedID 28277376

• Small-Volume Injections: Evaluation of Volume Administration Deviation From Intended Injection Volumes. Anesthesia and analgesia Muffly, M. K., Chen, M. I., Claure, R. E., Drover, D. R., Efron, B., Fitch, W. L., Hammer, G. B. 2017

  Abstract

  In the perioperative period, anesthesiologists and postanesthesia care unit (PACU) nurses routinely prepare and administer small-volume IV injections, yet the accuracy of delivered medication volumes in this setting has not been described. In this ex vivo study, we sought to characterize the degree to which small-volume injections (≤0.5 mL) deviated from the intended injection volumes among a group of pediatric anesthesiologists and pediatric postanesthesia care unit (PACU) nurses. We hypothesized that as the intended injection volumes decreased, the deviation from those intended injection volumes would increase.Ten attending pediatric anesthesiologists and 10 pediatric PACU nurses each performed a series of 10 injections into a simulated patient IV setup. Practitioners used separate 1-mL tuberculin syringes with removable 18-gauge needles (Becton-Dickinson & Company, Franklin Lakes, NJ) to aspirate 5 different volumes (0.025 mL, 0.05 mL, 0.1 mL, 0.25 mL, and 0.5 mL) of 0.25 mM Lucifer Yellow (LY) fluorescent dye constituted in saline (Sigma Aldrich, St. Louis, MO) from a rubber-stoppered vial. Each participant then injected the specified volume of LY fluorescent dye via a 3-way stopcock into IV tubing with free-flowing 0.9% sodium chloride (10 mL/min). The injected volume of LY fluorescent dye and 0.9% sodium chloride then drained into a collection vial for laboratory analysis. Microplate fluorescence wavelength detection (Infinite M1000; Tecan, Mannedorf, Switzerland) was used to measure the fluorescence of the collected fluid. Administered injection volumes were calculated based on the fluorescence of the collected fluid using a calibration curve of known LY volumes and associated fluorescence. To determine whether deviation of the administered volumes from the intended injection volumes increased at lower injection volumes, we compared the proportional injection volume error (loge [administered volume/intended volume]) for each of the 5 injection volumes using a linear regression model. Analysis of variance was used to determine whether the absolute log proportional error differed by the intended injection volume. Interindividual and intraindividual deviation from the intended injection volume was also characterized.As the intended injection volumes decreased, the absolute log proportional injection volume error increased (analysis of variance, P < .0018). The exploratory analysis revealed no significant difference in the standard deviations of the log proportional errors for injection volumes between physicians and pediatric PACU nurses; however, the difference in absolute bias was significantly higher for nurses with a 2-sided significance of P = .03.Clinically significant dose variation occurs when injecting volumes ≤0.5 mL. Administering small volumes of medications may result in unintended medication administration errors.

  View details for DOI 10.1213/ANE.0000000000001976

  View details for PubMedID 28338490

• Small-Volume Injections: Evaluation of Volume Administration Deviation From Intended Injection Volumes. Anesthesia and analgesia Muffly, M. K., Chen, M. I., Claure, R. E., Drover, D. R., Efron, B., Fitch, W. L., Hammer, G. B. 2017

  Abstract

  In the perioperative period, anesthesiologists and postanesthesia care unit (PACU) nurses routinely prepare and administer small-volume IV injections, yet the accuracy of delivered medication volumes in this setting has not been described. In this ex vivo study, we sought to characterize the degree to which small-volume injections (≤0.5 mL) deviated from the intended injection volumes among a group of pediatric anesthesiologists and pediatric postanesthesia care unit (PACU) nurses. We hypothesized that as the intended injection volumes decreased, the deviation from those intended injection volumes would increase.Ten attending pediatric anesthesiologists and 10 pediatric PACU nurses each performed a series of 10 injections into a simulated patient IV setup. Practitioners used separate 1-mL tuberculin syringes with removable 18-gauge needles (Becton-Dickinson & Company, Franklin Lakes, NJ) to aspirate 5 different volumes (0.025 mL, 0.05 mL, 0.1 mL, 0.25 mL, and 0.5 mL) of 0.25 mM Lucifer Yellow (LY) fluorescent dye constituted in saline (Sigma Aldrich, St. Louis, MO) from a rubber-stoppered vial. Each participant then injected the specified volume of LY fluorescent dye via a 3-way stopcock into IV tubing with free-flowing 0.9% sodium chloride (10 mL/min). The injected volume of LY fluorescent dye and 0.9% sodium chloride then drained into a collection vial for laboratory analysis. Microplate fluorescence wavelength detection (Infinite M1000; Tecan, Mannedorf, Switzerland) was used to measure the fluorescence of the collected fluid. Administered injection volumes were calculated based on the fluorescence of the collected fluid using a calibration curve of known LY volumes and associated fluorescence. To determine whether deviation of the administered volumes from the intended injection volumes increased at lower injection volumes, we compared the proportional injection volume error (loge [administered volume/intended volume]) for each of the 5 injection volumes using a linear regression model. Analysis of variance was used to determine whether the absolute log proportional error differed by the intended injection volume. Interindividual and intraindividual deviation from the intended injection volume was also characterized.As the intended injection volumes decreased, the absolute log proportional injection volume error increased (analysis of variance, P < .0018). The exploratory analysis revealed no significant difference in the standard deviations of the log proportional errors for injection volumes between physicians and pediatric PACU nurses; however, the difference in absolute bias was significantly higher for nurses with a 2-sided significance of P = .03.Clinically significant dose variation occurs when injecting volumes ≤0.5 mL. Administering small volumes of medications may result in unintended medication administration errors.

  View details for DOI 10.1213/ANE.0000000000001976

  View details for PubMedID 28338490

• Pharmacodynamic Analysis of Morphine Time-to-Remedication Events in Infants and Young Children After Congenital Heart Surgery. Clinical pharmacokinetics Elkomy, M. H., Drover, D. R., Galinkin, J. L., Hammer, G. B., Glotzbach, K. L. 2016; 55 (10): 1217-1226

  Abstract

  The aim of this study was to characterize the relationship between morphine plasma concentration and repeated time to postoperative remedication events in children undergoing cardiac surgery.Data from our previously published study of morphine pharmacokinetics were utilized in this pharmacodynamic study. A population survival analysis based on hazard functions was undertaken in NONMEM(®).Hazard was best described by a Gompertz function changing in steps over time. Concentration and age were the only predictors of the hazard function. Concentration producing 50 % reduction in hazard was 19.6 (bootstrap 95 % confidence interval 5.90-49.5 ng/ml). The hazard ratio for a 1-year-old child to a 1-month-old child was 1.91 (1.35-2.86). Sensitivity to morphine decreased with age and leveled off after 1-year of life. Morphine sulfate doses >0.1 mg/kg did not noticeably increase tolerable pain durations.Time to remedication is a clinically useful endpoint for assessing opioid-induced analgesia. Sensitivity to morphine treatment is age-dependent. Morphine sulfate doses of 0.1-0.2 mg/kg are adequate for the management of postoperative pain in children. Our findings may help avoid unnecessary large morphine doses in children.

  View details for DOI 10.1007/s40262-016-0398-z

  View details for PubMedID 27098060

• Pharmacokinetics of Morphine and Its Metabolites in Infants and Young Children After Congenital Heart Surgery AAPS JOURNAL Elkomy, M. H., Drover, D. R., Glotzbach, K. L., Galinkin, J. L., Frymoyer, A., Su, F., Hammer, G. B. 2016; 18 (1): 124-133

  Abstract

  The objective of this study was to characterize morphine glucuronidation in infants and children following cardiac surgery for possible treatment individualization in this population. Twenty children aged 3 days to 6 years, admitted to the cardiovascular intensive care unit after congenital heart surgery, received an intravenous (IV) loading dose of morphine (0.15 mg/kg) followed by subsequent intermittent IV bolus doses based on a validated pain scale. Plasma samples were collected over 6 h after the loading dose and randomly after follow-up doses to measure morphine and its major metabolite concentrations. A population pharmacokinetic model was developed with the non-linear mixed effects software NONMEM. Parent disposition was adequately described by a linear two-compartment model. Effect of growth (size and maturation) on morphine parameters was accounted for by allometric body weight-based models. An intermediate compartment with Emax model best characterized glucuronide concentrations. Glomerular filtration rate was identified as a significant predictor of glucuronide formation time delay and maximum concentrations. Clearance of morphine in children with congenital heart disease is comparable to that reported in children without cardiac abnormalities of similar age. Children 1-6 months of age need higher morphine doses per kilogram to achieve an area under concentration-time curve comparable to that in older children. Pediatric patients with renal failure receiving morphine therapy are at increased risk of developing opioid toxicity due to accumulation of morphine metabolites.

  View details for DOI 10.1208/s12248-015-9826-5

  View details for Web of Science ID 000367529900010

  View details for PubMedCentralID PMC4706285

• Pharmacokinetics of Morphine and Its Metabolites in Infants and Young Children After Congenital Heart Surgery. The AAPS journal Elkomy, M. H., Drover, D. R., Glotzbach, K. L., Galinkin, J. L., Frymoyer, A., Su, F., Hammer, G. B. 2016; 18 (1): 124-33

  Abstract

  The objective of this study was to characterize morphine glucuronidation in infants and children following cardiac surgery for possible treatment individualization in this population. Twenty children aged 3 days to 6 years, admitted to the cardiovascular intensive care unit after congenital heart surgery, received an intravenous (IV) loading dose of morphine (0.15 mg/kg) followed by subsequent intermittent IV bolus doses based on a validated pain scale. Plasma samples were collected over 6 h after the loading dose and randomly after follow-up doses to measure morphine and its major metabolite concentrations. A population pharmacokinetic model was developed with the non-linear mixed effects software NONMEM. Parent disposition was adequately described by a linear two-compartment model. Effect of growth (size and maturation) on morphine parameters was accounted for by allometric body weight-based models. An intermediate compartment with Emax model best characterized glucuronide concentrations. Glomerular filtration rate was identified as a significant predictor of glucuronide formation time delay and maximum concentrations. Clearance of morphine in children with congenital heart disease is comparable to that reported in children without cardiac abnormalities of similar age. Children 1-6 months of age need higher morphine doses per kilogram to achieve an area under concentration-time curve comparable to that in older children. Pediatric patients with renal failure receiving morphine therapy are at increased risk of developing opioid toxicity due to accumulation of morphine metabolites.

  View details for DOI 10.1208/s12248-015-9826-5

  View details for PubMedID 26349564

  View details for PubMedCentralID PMC4706285

• Safety and Efficacy of Sodium Nitroprusside During Prolonged Infusion in Pediatric Patients PEDIATRIC CRITICAL CARE MEDICINE Hammer, G. B., Lewandowski, A., Drover, D. R., Rosen, D. A., Cohane, C., Anand, R., Mitchell, J., Reece, T., Schulman, S. R. 2015; 16 (5): 397-403

  Abstract

  Sodium nitroprusside is a direct-acting vasodilator used to lower blood pressure in the operating room and ICU. The efficacy of sodium nitroprusside has been analyzed in few pediatric randomized trials. This study assesses the efficacy and safety of sodium nitroprusside following at least 12 hours of IV infusion in children.Randomized, double-blind withdrawal to placebo study.ICUs.Pediatric patients younger than 17 years.Following 12-24 hours of open-label sodium nitroprusside titration, a blinded infusion of sodium nitroprusside or placebo was administered (at the stable rate used at the end of the open-label phase) for up to 30 minutes.The primary efficacy measure was whether control of mean arterial blood pressure was lost, that is, increased above ambient baseline for two consecutive minutes during the blinded phase. The proportion of patients who lost mean arterial blood pressure control in the placebo group (15/19; 79%) was significantly different than those in the sodium nitroprusside group (9/20; 45%) (p = 0.048). Three patients experienced rebound hypertension during the blinded phase, and all were in the placebo group. Serious adverse event rates were low (7/52; 13%), and in only one patient was the serious adverse event determined to be related to sodium nitroprusside by the site investigator. Fourteen patients (27%) had whole blood cyanide levels above 0.5 μg/mL, with high correlation (0.7) between infusion rate and cyanide levels, but there were few clinical signs of cyanide toxicity.Sodium nitroprusside is efficacious in maintaining mean arterial blood pressure control in children following a 12-hour infusion. Although a high proportion of patients were found to have elevated cyanide levels, toxicity was not observed.

  View details for DOI 10.1097/PCC.0000000000000383

  View details for Web of Science ID 000358289300001

• Safety and efficacy of sodium nitroprusside during prolonged infusion in pediatric patients. Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies Hammer, G. B., Lewandowski, A., Drover, D. R., Rosen, D. A., Cohane, C., Anand, R., Mitchell, J., Reece, T., Schulman, S. R. 2015; 16 (5): 397-403

  Abstract

  Sodium nitroprusside is a direct-acting vasodilator used to lower blood pressure in the operating room and ICU. The efficacy of sodium nitroprusside has been analyzed in few pediatric randomized trials. This study assesses the efficacy and safety of sodium nitroprusside following at least 12 hours of IV infusion in children.Randomized, double-blind withdrawal to placebo study.ICUs.Pediatric patients younger than 17 years.Following 12-24 hours of open-label sodium nitroprusside titration, a blinded infusion of sodium nitroprusside or placebo was administered (at the stable rate used at the end of the open-label phase) for up to 30 minutes.The primary efficacy measure was whether control of mean arterial blood pressure was lost, that is, increased above ambient baseline for two consecutive minutes during the blinded phase. The proportion of patients who lost mean arterial blood pressure control in the placebo group (15/19; 79%) was significantly different than those in the sodium nitroprusside group (9/20; 45%) (p = 0.048). Three patients experienced rebound hypertension during the blinded phase, and all were in the placebo group. Serious adverse event rates were low (7/52; 13%), and in only one patient was the serious adverse event determined to be related to sodium nitroprusside by the site investigator. Fourteen patients (27%) had whole blood cyanide levels above 0.5 μg/mL, with high correlation (0.7) between infusion rate and cyanide levels, but there were few clinical signs of cyanide toxicity.Sodium nitroprusside is efficacious in maintaining mean arterial blood pressure control in children following a 12-hour infusion. Although a high proportion of patients were found to have elevated cyanide levels, toxicity was not observed.

  View details for DOI 10.1097/PCC.0000000000000383

  View details for PubMedID 25715047

• Population pharmacokinetics of etomidate in neonates and infants with congenital heart disease BIOPHARMACEUTICS & DRUG DISPOSITION Su, F., El-Komy, M. H., Hammer, G. B., Frymoyer, A., Cohane, C. A., Drover, D. R. 2015; 36 (2): 104-114

  Abstract

  Etomidate is a rapid-onset, short-acting hypnotic medication administered for induction of anesthesia. It is currently approved by the Food and Drug Administration for use in older children and adults. Pharmacokinetic data to help guide dosing in neonates and infants is lacking.The aim of this study was to determine the pharmacokinetics of etomidate in neonates and infants with congenital heart disease undergoing cardiac surgery.Four neonates and sixteen infants, postnatal age 0.3 - 11.7 months, requiring open-heart surgery received 0.3 mg/kg of etomidate administered as a single intravenous dose prior to surgery. Blood sampling for plasma etomidate concentration occurred immediately following etomidate administration until the initiation of cardiopulmonary bypass. A population pharmacokinetic approach using nonlinear mixed-effects modeling was applied to characterize etomidate pharmacokinetics.The pharmacokinetics of etomidate was described by a two-compartment model with first-order elimination. An allometric weight-based model was applied to scale results to a 70 kg adult. Covariates including age and cardiac physiology were not found to significantly impact etomidate pharmacokinetics. The study population was found to have a central and intercompartmental clearance of 0.624 L/min/70-kg and 0.44 L/min/70-kg, respectively; central and peripheral distribution volume of 9.47 and 22.8 L/70-kg, respectively. Inter-individual variability was between 94-142% for all parameters and residual variability was 29%.The clearance of etomidate is lower in neonates and infants with congenital heart disease compared to published values for older children without congenital heart disease. In addition, etomidate pharmacokinetics is highly variable in this pediatric cardiac population. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1002/bdd.1924

  View details for PubMedID 25377074

• Population pharmacokinetics of ketamine in children with heart disease INTERNATIONAL JOURNAL OF PHARMACEUTICS Elkomy, M. H., Drover, D. R., Hammer, G. B., Galinkin, J. L., Ramamoorthy, C. 2015; 478 (1): 223-231

  Abstract

  This study aims at developing a population pharmacokinetic model for ketamine in children with cardiac diseases in order to rationalize an effective 2-h anesthetic medication, personalized based on cardiac function and age. Twenty-one children (6 months to 18 years old) were enrolled in this prospective, open label study. Ketamine 2mg/kg IV was administered and blood samples were then collected over 8h for ketamine assay. Pharmacokinetic data analysis using NONMEM, was undertaken. Ketamine pharmacokinetics was adequately described by a two-compartment linear disposition model. Typical population parameters were: total clearance: 60.6×(weight/70)(0.75)L/h, intercompartmental clearance: 73.2×(weight/70)(0.75)L/h, central distribution volume: 57.3×(weight/70)L, and peripheral distribution volume: 152×(weight/70)L. Ketamine clearance in children with pre-existing congenital heart disease was comparable to values reported in healthy subjects. Computer simulations indicated that an initial loading dose of ketamine 2mg/kg IV over 1min followed by a constant rate infusion of 6.3mg/kg/h for 29min, 4.5mg/kg/h from 30 to 80min, and 3.9mg/kg/h from 80 to 120min achieves and maintains anesthetic plasma level for 2h in children 1 year or older (weight ≥10kg).

  View details for DOI 10.1016/j.ijpharm.2014.11.026

  View details for Web of Science ID 000348621100026

• Population pharmacokinetics of ketamine in children with heart disease. International journal of pharmaceutics Elkomy, M. H., Drover, D. R., Hammer, G. B., Galinkin, J. L., Ramamoorthy, C. 2015; 478 (1): 223-231

  Abstract

  This study aims at developing a population pharmacokinetic model for ketamine in children with cardiac diseases in order to rationalize an effective 2-h anesthetic medication, personalized based on cardiac function and age. Twenty-one children (6 months to 18 years old) were enrolled in this prospective, open label study. Ketamine 2mg/kg IV was administered and blood samples were then collected over 8h for ketamine assay. Pharmacokinetic data analysis using NONMEM, was undertaken. Ketamine pharmacokinetics was adequately described by a two-compartment linear disposition model. Typical population parameters were: total clearance: 60.6×(weight/70)(0.75)L/h, intercompartmental clearance: 73.2×(weight/70)(0.75)L/h, central distribution volume: 57.3×(weight/70)L, and peripheral distribution volume: 152×(weight/70)L. Ketamine clearance in children with pre-existing congenital heart disease was comparable to values reported in healthy subjects. Computer simulations indicated that an initial loading dose of ketamine 2mg/kg IV over 1min followed by a constant rate infusion of 6.3mg/kg/h for 29min, 4.5mg/kg/h from 30 to 80min, and 3.9mg/kg/h from 80 to 120min achieves and maintains anesthetic plasma level for 2h in children 1 year or older (weight ≥10kg).

  View details for DOI 10.1016/j.ijpharm.2014.11.026

  View details for PubMedID 25448584

• Evaluation of sodium nitroprusside for controlled hypotension in children during surgery. Frontiers in pharmacology Drover, D. R., Hammer, G. B., Barrett, J. S., Cohane, C. A., Reece, T., Zajicek, A., Schulman, S. R. 2015; 6: 136-?

  Abstract

  (1) To define the onset and offset of the blood-pressure-lowering effects of sodium nitroprusside (SNP) for use in developing instructions for dose titration in children undergoing a surgical or medical procedure, and (2) to assess the safety of SNP administration in pediatric patients requiring controlled reduction of blood pressure.We conducted a randomized, double-blind, parallel-group, dose-ranging, effect-controlled, multicenter study of intravenous (IV) infusions of SNP in pediatric patients <17 years, who required controlled hypotension for at least 2 h while undergoing a surgical or medical procedure. A blinded SNP dose of 0.3, 1, 2, or 3 μg/kg/min was infused for 30 min, followed by open-label administration for at least 90 min. Both infusions were titrated to effect.The final intent-to-treat group comprised 203 patients. Significant reductions in mean arterial pressure (MAP) from baseline were observed for all four doses at 20 and 25 min after the start of infusion (p ≤ 0.009 and p ≤ 0.010 for each time, respectively). Overall, 98.5% of the patients achieved the target MAP; 72.9% first achieved the target MAP during the blinded infusion. The mean infusion rate at target MAP was 1.07 μg/kg/min.We determined that 0.3 μg/kg/m is a reasonable starting dose for SNP in pediatric patients requiring controlled hypotension. The infusion rate can then be increased to achieve the desired reduction in blood pressure. On the basis of our results, we found an average infusion rate of 1 μg/kg/min might be appropriate. Of note, no cyanide toxicity was reported, and no measureable cyanide levels were detected in any blood samples obtained during the study. http://clinicaltrials.gov/show/NCT00135668.

  View details for DOI 10.3389/fphar.2015.00136

  View details for PubMedID 26217225

• Airway and Respiratory Management ANESTHESIA FOR CONGENITAL HEART DISEASE, 3RD EDITION Stayer, S. A., Hammer, G. B., Andropoulos, D. B., Stayer, S., Mossad, E. B., MillerHance, W. C. 2015: 436–50

  View details for Web of Science ID 000385225800020

• Evaluation of sodium nitroprusside for controlled hypotension in children during surgery. Frontiers in pharmacology Drover, D. R., Hammer, G. B., Barrett, J. S., Cohane, C. A., Reece, T., Zajicek, A., Schulman, S. R. 2015; 6: 136-?

  View details for DOI 10.3389/fphar.2015.00136

  View details for PubMedID 26217225

• A hemodynamic model to guide blood pressure control during deliberate hypotension with sodium nitroprusside in children. Frontiers in pharmacology Barrett, J. S., Hirankarn, S., Holford, N., Hammer, G. B., Drover, D. R., Cohane, C. A., Anderson, B., Dombrowski, E., Reece, T., Zajicek, A., Schulman, S. R. 2015; 6: 151-?

  View details for DOI 10.3389/fphar.2015.00151

  View details for PubMedID 26283961

• A hemodynamic model to guide blood pressure control during deliberate hypotension with sodium nitroprusside in children. Frontiers in pharmacology Barrett, J. S., Hirankarn, S., Holford, N., Hammer, G. B., Drover, D. R., Cohane, C. A., Anderson, B., Dombrowski, E., Reece, T., Zajicek, A., Schulman, S. R. 2015; 6: 151-?

  Abstract

  Sodium nitroprusside (SNP) has been widely used to control blood pressure in infants and children. The goals of this analysis were to develop models that describe the hemodynamic response to SNP dosing in pediatric patients; examine sources of variation in dose-response, defining age, and size dependencies; and determine vulnerable populations or patient subtypes that may elicit dosing modifications. A multi-center, randomized, double-blinded, parallel-group, dose-ranging, effect-controlled study, followed by an open-label dose titration of an intravenous infusion of SNP was undertaken in 203 pediatric subjects, who required deliberate hypotension or controlled normotension during anesthesia. A total of 3464 MAP measurements collected from 202 patients during the study's blinded phase, including baseline measurements up to 6 min prior to the blinded were available for analysis. A population K-PD model was developed with a one-compartment model assumed for SNP. Size differences in CL and V of the effect compartment were described using theory-based allometry. An inhibitory sigmoidal Emax model was used to describe the effect of SNP. A power function of age was used to describe age-related differences in baseline MAP. A mixture model of two groups with low and high EC50 was used to explain variability in MAP response. Change in MAP was characterized by a linear disease progression slope during the blinded phase. In the final population model, CL and V increased with weight, and baseline MAP increased with age. The effect compartment half-life of SNP was 13.4 min. The infusion rate producing 50% of Emax (ER50) at steady state for high EC50, was 0.34 μg/kg/min and for low EC50 0.103 μg/kg/min. The K-PD model well-describes initial dosing of SNP under controlled circumstances; model-based dosing guidance agrees with current practice. An initial titration strategy supported via algorithm-based feedback should improve maintenance of target MAP.

  View details for DOI 10.3389/fphar.2015.00151

  View details for PubMedID 26283961

• THE PHARMACOKINETICS OF ETOMIDATE IN NEONATES AND INFANTS WITH CONGENITAL HEART DISEASE Su, F., Cohane, C., Drover, D., El-Komy, M., Frymoyer, A., Hammer, G. LIPPINCOTT WILLIAMS & WILKINS. 2014

  View details for Web of Science ID 000346211800623

• Predictors of Arterial Blood Pressure Control During Deliberate Hypotension with Sodium Nitroprusside in Children ANESTHESIA AND ANALGESIA Spielberg, D. R., Barrett, J. S., Hammer, G. B., Drover, D. R., Reece, T., Cohane, C. A., Schulman, S. R. 2014; 119 (4): 867-874

  Abstract

  Sodium nitroprusside (SNP) is used to decrease arterial blood pressure (BP) during certain surgical procedures. There are limited data regarding efficacy of BP control with SNP. There are no data on patient and clinician factors that affect BP control. We evaluated the dose-response relationship of SNP in infants and children undergoing major surgery and performed a quantitative assessment of BP control.One hundred fifty-three subjects at 7 sites received a blinded infusion followed by open-label SNP during operative procedures requiring controlled hypotension. SNP was administered by continuous infusion and titrated to maintain BP control (mean arterial BP [MAP] within ±10% of clinician-defined target). BP was recorded using an arterial catheter. Statistical process control methodology was used to quantify BP control. A multivariable model assessed the effects of patient and procedural factors.BP was controlled an average 45.4% (SD 23.9%; 95% CI, 41.5%-49.18%) of the time. Larger changes in infusion rate were associated with worse BP control (7.99% less control for 1 μg·kg·min increase in average titration size, P = 0.0009). A larger difference between a patient's baseline and target MAP predicted worse BP control (0.93% worse control per 1-mm Hg increase in MAP difference, P = 0.0013). Both effects persisted in multivariable models.SNP was effective in reducing BP. However, BP was within the target range less than half of the time. No clinician or patient factors were predictive of BP control, although 2 inverse relationships were identified. These relationships require additional study and may be best coupled with exposure-response modeling to propose improved dosing strategies when using SNP for controlled hypotension in the pediatric population.

  View details for DOI 10.1213/ANE.0000000000000376

  View details for Web of Science ID 000341828200014

  View details for PubMedCentralID PMC4169308

• Predictors of arterial blood pressure control during deliberate hypotension with sodium nitroprusside in children. Anesthesia and analgesia Spielberg, D. R., Barrett, J. S., Hammer, G. B., Drover, D. R., Reece, T., Cohane, C. A., Schulman, S. R. 2014; 119 (4): 867-874

  Abstract

  Sodium nitroprusside (SNP) is used to decrease arterial blood pressure (BP) during certain surgical procedures. There are limited data regarding efficacy of BP control with SNP. There are no data on patient and clinician factors that affect BP control. We evaluated the dose-response relationship of SNP in infants and children undergoing major surgery and performed a quantitative assessment of BP control.One hundred fifty-three subjects at 7 sites received a blinded infusion followed by open-label SNP during operative procedures requiring controlled hypotension. SNP was administered by continuous infusion and titrated to maintain BP control (mean arterial BP [MAP] within ±10% of clinician-defined target). BP was recorded using an arterial catheter. Statistical process control methodology was used to quantify BP control. A multivariable model assessed the effects of patient and procedural factors.BP was controlled an average 45.4% (SD 23.9%; 95% CI, 41.5%-49.18%) of the time. Larger changes in infusion rate were associated with worse BP control (7.99% less control for 1 μg·kg·min increase in average titration size, P = 0.0009). A larger difference between a patient's baseline and target MAP predicted worse BP control (0.93% worse control per 1-mm Hg increase in MAP difference, P = 0.0013). Both effects persisted in multivariable models.SNP was effective in reducing BP. However, BP was within the target range less than half of the time. No clinician or patient factors were predictive of BP control, although 2 inverse relationships were identified. These relationships require additional study and may be best coupled with exposure-response modeling to propose improved dosing strategies when using SNP for controlled hypotension in the pediatric population.

  View details for DOI 10.1213/ANE.0000000000000376

  View details for PubMedID 25099924

• The pharmacokinetics of methadone and its metabolites in neonates, infants, and children PEDIATRIC ANESTHESIA Ward, R. M., Drover, D. R., Hammer, G. B., Stemland, C. J., Kern, S., Tristani-Firouzi, M., Lugo, R. A., Satterfield, K., Anderson, B. J. 2014; 24 (6): 591-601

  Abstract

  The lack of methadone pharmacokinetic data in children and neonates restrains dosing to achieve the target concentration in these populations. A minimum effective analgesic concentration of methadone in opioid naïve adults is 0.058 mg·l(-1) , while no withdrawal symptoms were observed in neonates suffering opioid withdrawal if plasma concentrations of methadone were above 0.06 mg·l(-1) . The racemate of methadone which is commonly used in pediatric and anesthetic care is metabolized to 2-ethylidine-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) and 2-ethyl-5-methyl-3,3-diphenylpyrroline (EMDP).Data from four studies (age 33-week PMA-15 years) were pooled (n = 56) for compartment analysis using nonlinear mixed effects modeling. Parameter estimates were standardized to a 70-kg person using an allometric model approach. Investigation was made of the racemate and metabolite (EDDP and EMDP) dispositions. In addition, neonatal data (n = 7) allowed further study of R- and S-enantiomer pharmacokinetics.A three-compartment linear disposition model best described the observed time-concentration profiles with additional compartments for metabolites. Population parameter estimates (between-subject variability) were central volume (V1) 21.5 (29%) l.70 kg(-1) , peripheral volumes of distribution V2 75.1 (23%) l.70 kg(-1) and V3 484 (8%) l.70 kg(-1) , clearance (CL) 9.45 (11%) l·h(-1) .70 kg(-1) , and intercompartment clearances Q2 325 (21%) l·h(-1) .70 kg(-1) and Q3 136 (14%) l·h(-1) .70 kg(-1) . EDDP formation clearance was 9.1 (11%) l·h(-1) .70 kg(-1) , formation clearance of EMDP from EDDP 7.4 (63%) l·h(-1) .70 kg(-1) , elimination clearance of EDDP was 40.9 (26%) l·h(-1) .70 kg(-1) and the rate constant for intermediate compartments 2.17 (43%) h(-1) .Current pharmacokinetic parameter estimates in children and neonates are similar to those reported in adults. There was no clearance maturation with age. Neonatal enantiomer clearances were similar to those described in adults. A regimen of 0.2 mg·kg(-1) per 8 h in neonates achieves a target concentration of 0.06 mg·l(-1) within 36 h. Infusion, rather than intermittent dosing, should be considered if this target is to be achieved in older children after cardiac surgery.

  View details for DOI 10.1111/pan.12385

  View details for Web of Science ID 000335753700007

  View details for PubMedID 24666686

  View details for PubMedCentralID PMC4016164

• Reply to Breschan et al, re 'central venus catheter placement in children'. Paediatric anaesthesia Kamra, K., Hammer, G. 2014; 24 (3): 345-?

  View details for DOI 10.1111/pan.12352

  View details for PubMedID 24467577

• Anesthesia and the developing brain: relevance to the pediatric cardiac surgery. Brain sciences Wise-Faberowski, L., Quinonez, Z. A., Hammer, G. B. 2014; 4 (2): 295-310

  Abstract

  Anesthetic neurotoxicity has been a hot topic in anesthesia for the past decade. It is of special interest to pediatric anesthesiologists. A subgroup of children potentially at greater risk for anesthetic neurotoxicity, based on a prolonged anesthetic exposure early in development, are those children receiving anesthesia for surgical repair of congenital heart disease. These children have a known risk of neurologic deficit after cardiopulmonary bypass for surgical repair of congenital heart disease. Yet, the type of anesthesia used has not been considered as a potential etiology for their neurologic deficits. These children not only receive prolonged anesthetic exposure during surgical repair, but also receive repeated anesthetic exposures during a critical period of brain development. Their propensity to abnormal brain development, as a result of congenital heart disease, may modify their risk of anesthetic neurotoxicity. This review article provides an overview of anesthetic neurotoxicity from the perspective of a pediatric cardiac anesthesiologist and provides insight into basic science and clinical investigations as it relates to this unique group of children who have been studied over several decades for their risk of neurologic injury.

  View details for DOI 10.3390/brainsci4020295

  View details for PubMedID 24961762

• Thrombotic endotracheal tube occlusion after administration of recombinant factor VIIa. Journal of cardiothoracic and vascular anesthesia Benkwitz, C., Hammer, G. B. 2013; 27 (6): 1330-1333

  View details for DOI 10.1053/j.jvca.2012.07.003

  View details for PubMedID 22959153

• Thrombotic Endotracheal Tube Occlusion After Administration Factor VIIa JOURNAL OF CARDIOTHORACIC AND VASCULAR ANESTHESIA Benkwitz, C., Hammer, G. B. 2013; 27 (6): 1330-1333

  View details for DOI 10.1053/j.jvca.2012.07.003

  View details for Web of Science ID 000328181700040

• Central venous catheter placement in children: 'How good is good enough?' PEDIATRIC ANESTHESIA Kamra, K., Hammer, G. B. 2013; 23 (11): 971–73

  View details for PubMedID 24088200

• The effects of ketamine on dexmedetomidine-induced electrophysiologic changes in children. Paediatric anaesthesia Char, D., Drover, D. R., Motonaga, K. S., Gupta, S., Miyake, C. Y., Dubin, A. M., Hammer, G. B. 2013; 23 (10): 898-905

  Abstract

  BACKGROUND: Dexmedetomidine is an alpha2-adrenergic agonist used for sedation and analgesia in children. We previously showed that dexmedetomidine depresses sinus and AV nodal function resulting in adverse hemodynamic effects such as bradycardia and increased blood pressure. We hypothesized that these effects of dexmedetomidine might be antagonized by co-administration of ketamine, which has sympathomimetic properties. METHODS: Twenty-two children (ages 5-17 years) undergoing electrophysiologic (EP) study and ablation for supraventricular tachycardia were enrolled. Patients were kept sedated with continuous infusion of propofol at a fixed rate. Hemodynamic and EP parameters were measured before and after a loading dose of dexmedetomidine (1 μg·kg(-1) ). A continuous infusion of dexmedetomidine (0.7 μg·kg(-1) ·h(-1) ) was initiated and a ketamine loading dose (1 mg·kg(-1) ), followed by continuous infusion (1 mg·kg(-1) ·h(-1) ), was given. A repeat set of hemodynamic and EP parameters were then measured at the time of projected peak tissue concentration for both drugs. RESULTS: A significant increase in mean arterial pressure (MAP) was seen compared with baseline after loading of dexmedetomidine. This returned to baseline after co-administration of ketamine (mean difference between baseline and after ketamine 1.8 mmHg; 95%CI, -7.8 to 4.3; P = <0.001). A decrease in heart rate was seen after dexmedetomidine followed by a return to baseline after co-administration of ketamine (mean difference between baseline and after ketamine -6.5 bpm; 95%CI, -11.2 to -1.8; P = 0.005). Sinus node recovery time was lengthened after dexmedetomidine but returned to baseline after ketamine (mean difference between baseline and after ketamine -16.2 ms; 95%CI, -63 to 30; P = 0.014). QT was prolonged after dexmedetomidine and returned to baseline after ketamine (mean difference between baseline and after ketamine -34.2 ms; 95%CI, -48.4 to -20.2; P = 0.004). AV nodal effective refractory period was also impaired after dexmedetomidine and showed weak evidence for return to baseline function after ketamine (mean difference between baseline and after ketamine -22.8 ms; 95%CI, -40.2 to -5.2; P = 0.069). CONCLUSION: The concurrent use of ketamine may mitigate the negative chronotropic effects of dexmedetomidine.

  View details for DOI 10.1111/pan.12143

  View details for PubMedID 23506472

• Comparison of a New Cobinamide-Based Method to a Standard Laboratory Method for Measuring Cyanide in Human Blood JOURNAL OF ANALYTICAL TOXICOLOGY Swezey, R., Shinn, W., Green, C., Drover, D. R., Hammer, G. B., Schulman, S. R., Zajicek, A., Jett, D. A., Boss, G. R. 2013; 37 (6): 382-385

  Abstract

  Most hospital laboratories do not measure blood cyanide concentrations, and samples must be sent to reference laboratories. A simple method is needed for measuring cyanide in hospitals. The authors previously developed a method to quantify cyanide based on the high binding affinity of the vitamin B12 analog, cobinamide, for cyanide and a major spectral change observed for cyanide-bound cobinamide. This method is now validated in human blood, and the findings include a mean inter-assay accuracy of 99.1%, precision of 8.75% and a lower limit of quantification of 3.27 µM cyanide. The method was applied to blood samples from children treated with sodium nitroprusside and it yielded measurable results in 88 of 172 samples (51%), whereas the reference laboratory yielded results in only 19 samples (11%). In all 19 samples, the cobinamide-based method also yielded measurable results. The two methods showed reasonable agreement when analyzed by linear regression, but not when analyzed by a standard error of the estimate or paired t-test. Differences in results between the two methods may be because samples were assayed at different times on different sample types. The cobinamide-based method is applicable to human blood, and can be used in hospital laboratories and emergency rooms.

  View details for DOI 10.1093/jat/bkt037

  View details for Web of Science ID 000321456900010

  View details for PubMedID 23653045

  View details for PubMedCentralID PMC3708715

• Sodium nitroprusside is not associated with metabolic acidosis during intraoperative infusion in children BMC ANESTHESIOLOGY Hammer, G. B., Connolly, S. G., Schulman, S. R., Lewandowski, A., Cohane, C., Reece, T. L., Anand, R., Mitchell, J., Drover, D. R. 2013; 13

  Abstract

  Sodium nitroprusside (SNP) is a potent vasodilator that has been used to induce deliberate hypotension in children during surgery involving significant blood loss, including craniofacial and spinal fusion procedures. SNP metabolism liberates cyanide, which may cause interference with cellular energy metabolism, leading to metabolic acidosis and central nervous system injury. We performed a retrospective, case-control study to determine whether the short-term intra-operative use of SNP for deliberate hypotension is associated with metabolic acidosis in children undergoing surgical procedures for craniofacial or spinal anomalies. Cyanide and thiocyanate concentrations were also recorded in patients who received SNP.Data from 166 children undergoing craniofacial and spinal fusion surgery between 2005 and 2010 at Lucile Packard Children's Hospital (LPCH) at Stanford were analyzed. Records from 60 patients who received SNP (SNP group) as part of a multicenter, randomized, double-blind study were compared with records from 106 eligible patients who had blood pressure reduction using anesthetic agents and did not receive SNP (control group). Metabolic acidosis was defined as serum bicarbonate (HCO3) < 18.5 mEq/L. Whole blood CN, plasma thiocyanate and urinary thiocyanate concentrations were measured in patients in the SNP group. Differences in metabolic acidosis rates between the SNP and control groups were assessed through a test of noninferiority in the rate for the SNP group with a noninferiority threshold of 0.2. A z-test was used to test the null hypothesis. The alternative hypothesis was that the difference in these rates was less than 0.2. The same noninferiority threshold of 0.2 was also used to perform separate, secondary tests for noninferiority in the proportion of patients with HCO3 levels below 18.5 mEq/L and the proportion of patients who required HCO3 administration.Fewer patients in the SNP group experienced metabolic acidosis compared to the control group (31.7% vs. 36.8%, respectively; p < .001). No whole blood CN levels above the lower limit of quantification were detected in any of the 51 patients with validated CN data. Plasma and urinary thiocyanate levels were also low.Our findings suggest that SNP, when used for short-term deliberate hypotension, does not cause an increased incidence of metabolic acidosis compared with the use of anesthetic agents alone.Trial registration number: NCT00135668.

  View details for DOI 10.1186/1471-2253-13-9

  View details for Web of Science ID 000318602200001

  View details for PubMedID 23631460

  View details for PubMedCentralID PMC3648371

• Anesthesia and the Developing Brain: Relevance to the Pediatric Cardiac Surgery Brain Sci Wise-Faberowski , L. 2013; 4 (2): 295-310

  View details for DOI 10.3390/brainsci4020295

• The Pharmacokinetics of Ketorolac After Single Postoperative Intranasal Administration in Adolescent Patients ANESTHESIA AND ANALGESIA Drover, D. R., Hammer, G. B., Anderson, B. J. 2012; 114 (6): 1270-1276

  Abstract

  Ketorolac tromethamine (ketorolac) administration reduces postoperative opioid requirements. The pharmacokinetic characteristics of intranasal ketorolac tromethamine in children have not been characterized. Our objective of this study was to determine the pharmacokinetics of a single intranasal dose of ketorolac in adolescent patients.Twenty surgical patients, ages 12 to 17 years, were enrolled. After surgery, subjects received intranasal ketorolac 15 mg (weight ≤50 kg) or 30 mg (weight >50 kg) using a proprietary administration system. Blood samples were obtained for ketorolac assay at baseline (within 15 minutes before the dose) and at 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours after the dose. A population analysis was undertaken using nonlinear mixed-effects models. Parameter estimates were standardized to a 70-kg person.The intranasal dosing in adolescents was well tolerated with minimal adverse effects. A 1-compartment model with first-order absorption and elimination was satisfactory to describe time-concentration profiles. Population parameter estimates (between subject variability) were clearance (CL/F) 2.05 L/h (60.5%), volume of distribution (V/F) 15.2 L (32.4%), absorption half-life (t(1/2)abs) 0.173 hour (25.0%). Time to peak concentration (Tmax) was 52 minutes (SD 6 minutes).Administration of ketorolac by the intranasal route resulted in a rapid increase in plasma concentration and may be a useful therapeutic alternative to IV injection in adolescents because plasma concentrations attained with the device are likely to be analgesic (investigational new drug no. 62,829).

  View details for DOI 10.1213/ANE.06013e31824f92c2

  View details for PubMedID 22467894

• A PHASE III, RANDOMIZED, DOUBLE-BLIND, DOSE-CONTROLLED, MULTICENTER STUDY OF THE SAFETY AND EFFICACY OF DEXMEDETOMIDINE IN MECHANICALLY VENTILATED CHILDREN Hammer, G. B., Soliman, D. E., Newth, C., Boriosi, J., Schulman, S. LIPPINCOTT WILLIAMS & WILKINS. 2012

  View details for Web of Science ID 000209846600218

• Sodium Nitroprusside Is Not Associated with Metabolic Acidosis During Intraoperative Infusion in Children Hammer, G., Drover, D., Connolly, S., Cohane, C., Schulman, S. OXFORD UNIV PRESS. 2012: 293

  View details for Web of Science ID 000302299100491

• Cardiomyopathy in childhood CURRENT OPINION IN ANESTHESIOLOGY Williams, G. D., Hammer, G. B. 2011; 24 (3): 289-300

  Abstract

  Cardiomyopathy is an important cause of heart failure and a major indication for heart transplantation in children. Unfortunately, there is a paucity of literature to guide the anesthesiologist who cares for these high-risk children. This review describes the cardiomyopathy phenotypes that occur in children and the factors that are associated with clinical outcomes and perioperative complications. Anesthesia considerations will be reviewed.During the past decade, there has been a dramatic increase in knowledge related to cardiomyopathy. New genotypes and phenotypes are recognized and new therapies have been devised. Multicenter pediatric cardiomyopathy registries are obtaining data essential for enhanced understanding of the disease.The diverse spectrum and complexity of pediatric cardiomyopathies mandate a thorough appreciation of the cardiac pathophysiology pertinent to an individual child's perioperative management. Important issues include multisystem disease associated with syndromic or genetic disorders, appropriate preoperative patient assessment to adequately characterize patient risk and guide therapy, and intraoperative and postoperative care plans that target optimal outcomes.

  View details for DOI 10.1097/ACO.0b013e3283462257

  View details for PubMedID 21478741

• Cardiomyopathy and heart failure in children: anesthetic implications PEDIATRIC ANESTHESIA Rosenthal, D. N., Hammer, G. B. 2011; 21 (5): 577-584

  Abstract

  The purpose of this article is to provide a brief but systematic overview of heart failure and cardiomyopathy in children and the anesthetic management of these patients. We will begin with disease definitions and descriptions of the disorders. Our review will include the epidemiology and etiology of the more prevalent underlying causes of heart failure, the principal pathophysiology of the specific cardiomyopathies, as well as the common therapies in use today in both inpatient and outpatient settings. Important implications for anesthetic management will be highlighted.

  View details for DOI 10.1111/j.1460-9592.2011.03561.x

  View details for PubMedID 21481080

• A sensitive assay for the quantification of morphine and its active metabolites in human plasma and dried blood spots using high-performance liquid chromatography-tandem mass spectrometry ANALYTICAL AND BIOANALYTICAL CHEMISTRY Clavijo, C. F., Hoffman, K. L., Thomas, J. J., Carvalho, B., Chu, L. F., Drover, D. R., Hammer, G. B., Christians, U., Galinkin, J. L. 2011; 400 (3): 715-728

  Abstract

  Opioids such as morphine are the cornerstone of pain treatment. The challenge of measuring the concentrations of morphine and its active metabolites in order to assess human pharmacokinetics and monitor therapeutic drugs in children requires assays with high sensitivity in small blood volumes. We developed and validated a semi-automated LC-MS/MS assay for the simultaneous quantification of morphine and its active metabolites morphine 3β-glucuronide (M3G) and morphine 6β-glucuronide (M6G) in human plasma and in dried blood spots (DBS). Reconstitution in water (DBS only) and addition of a protein precipitation solution containing the internal standards were the only manual steps. Morphine and its metabolites were separated on a Kinetex 2.6-μm PFP analytical column using an acetonitrile/0.1% formic acid gradient. The analytes were detected in the positive multiple reaction mode. In plasma, the assay had the following performance characteristics: range of reliable response of 0.25-1000 ng/mL (r(2) > 0.99) for morphine, 1-1,000 ng/mL (r(2) > 0.99) for M3G, and 2.5-1,000 ng/mL for M6G. In DBS, the assay had a range of reliable response of 1-1,000 ng/mL (r(2) > 0.99) for morphine and M3G, and of 2.5-1,000 ng/mL for M6G. For inter-day accuracy and precision for morphine, M3G and M6G were within 15% of the nominal values in both plasma and DBS. There was no carryover, ion suppression, or matrix interferences. The assay fulfilled all predefined acceptance criteria, and its sensitivity using DBS samples was adequate for the measurement of pediatric pharmacokinetic samples using a small blood of only 20-50 μL.

  View details for DOI 10.1007/s00216-011-4775-z

  View details for Web of Science ID 000289297000015

  View details for PubMedID 21400080

• POPULATION K-PD MODEL OF SODIUM NITROPRUSSIDE IN CHILDREN Hirankarn, S., Hammer, G. B., Schulman, S. R., Drover, D. R., Dombrowsky, E., Zajicek, A., Cohane, C., Barrett, J. S. NATURE PUBLISHING GROUP. 2011: S55

  View details for Web of Science ID 000286644100176

• A sensitive assay for the quantification of morphine and its active metabolites in human plasma and dried blood spots using high-performance liquid chromatography-tandem mass spectrometry Anal Bioanal Chem. Clavijo CF, Hoffman KL, Thomas JJ, Carvalho B, Chu LF, Drover DR, Hammer GB, Christians U, Galinkin JL 2011; 400: 715-28
• Dexmedetomidine: pediatric pharmacology, clinical uses and safety EXPERT OPINION ON DRUG SAFETY Su, F., Hammer, G. B. 2011; 10 (1): 55-66

  Abstract

  Dexmedetomidine is an α(2)-adrenoceptor agonist with sedative, anxiolytic and analgesic properties. It is used off-label in pediatric patients due to its efficacy and lack of adverse respiratory effects. Dexmedetomidine may cause severe circulatory complications in adults. Despite its popularity, the safety of dexmedetomidine in the pediatric population has not been extensively studied.This article reviews the current literature (up to 2010) focusing on applications and safety of dexmedetomidine administered to pediatric patients.Dexmedetomidine is a useful sedative and anxiolytic drug in the pediatric intensive care unit as well as during diagnostic and therapeutic procedures. Deleterious effects of dexmedetomidine include hypotension and bradycardia. Additionally, hypertension may occur during the "loading dose" or with high infusion rates. Few studies have been performed to evaluate the safety of dexmedetomidine in pediatrics. The development of tolerance and withdrawal has not been studied in children.Despite its favorable respiratory profile, dexmedetomidine may cause deleterious cardiovascular effects. Close monitoring of circulatory dynamics and judicious titration is recommended. Further studies are needed to better define adverse effects following long-term infusions as well as in special populations such as pre-term infants.

  View details for DOI 10.1517/14740338.2010.512609

  View details for PubMedID 20718689

• Safety and Population Pharmacokinetic Analysis of Intravenous Acetaminophen in Neonates, Infants, Children and Adolescents with Pain or Fever. J Pediatr Pharmacol Ther. Zuppa AF, Hammer GB, Barrett JS, Kenney BF, Kassir N, Mouksassi S, Royal MA. 2011; 16 (4): 246-61
• Response to: Airway responses to desflurane during maintenance of anesthesia and recovery in children with laryngeal mask airways PEDIATRIC ANESTHESIA Hannallah, R. S. 2010; 20 (10): 962–63

  View details for DOI 10.1111/j.1460-9592.2010.03400.x

  View details for Web of Science ID 000281949800012

  View details for PubMedID 20849506

• Airway responses to desflurane with laryngeal mask airways in children PEDIATRIC ANESTHESIA Lerman, J., Hammer, G. 2010; 20 (10): 963-+

  View details for DOI 10.1111/j.1460-9592.2010.03386.x

  View details for Web of Science ID 000281949800013

• SAS-BASED HEMODYNAMIC CONTROL CHARTS FOR THE MANAGEMENT OF NITROPRUSSIDE IN CHILDREN Dombrowsky, E. L., Jayaraman, B., Schulman, S. R., Hammer, G. B., Drover, D., Barrett, J. S. SAGE PUBLICATIONS INC. 2010: 1076

  View details for Web of Science ID 000281858000080

• Airway responses to desflurane during maintenance of anesthesia and recovery in children with laryngeal mask airways PEDIATRIC ANESTHESIA Lerman, J., Hammer, G. B., Verghese, S., Ehlers, M., Khalil, S. N., Betts, E., Trillo, R., Deutsch, J. 2010; 20 (6): 495-505

  Abstract

  We sought to characterize the airway responses to desflurane during maintenance of and emergence from anesthesia in children whose airways were supported with laryngeal mask airways (LMAs).Four hundred healthy children were randomized in a 3 : 1 ratio to either desflurane or isoflurane (reference group) during anesthetic maintenance. After induction of anesthesia, anesthesia was maintained with the designated anesthetic. The investigator chose the airway (LMA and facemask), ventilation strategy and when to remove the LMA. The incidence of airway events during maintenance, emergence and recovery was recorded.Ninety percent of children received LMAs. The frequency of major airway events after desflurane (9%) was similar to that after isoflurane (4%) (number needed to harm [NNH] 20), although the frequency of major events after the LMA was removed during deep desflurane anesthesia (15%) was greater than during awake removal (5%) (NNH 10) (P < 0.006) and during deep isoflurane removal (2%) (NNH 8) (P < 0.03). The frequency of airway events of any severity after desflurane was greater than that after isoflurane (39% vs 27%) (P < 0.05). The frequencies of laryngospasm and coughing of any severity after desflurane were greater than those after isoflurane (13% vs 5% and 26% vs 14%, respectively) (P < 0.05).When an LMA is used during desflurane anesthesia in children, fewer airway events occur when it is removed when the child is awake. Although the time to discharge from recovery was not delayed and no child required overnight admission, caution should be exercised when using an LMA in children who are anesthetized with desflurane.

  View details for DOI 10.1111/j.1460-9592.2010.03305.x

  View details for Web of Science ID 000277981700003

  View details for PubMedID 20456065

• Perioperative complications in children with pulmonary hypertension undergoing general anesthesia with ketamine PEDIATRIC ANESTHESIA Williams, G. D., Maan, H., Ramamoorthy, C., Kamra, K., Bratton, S. L., Bair, E., Kuan, C. C., Hammer, G. B., Feinstein, J. A. 2010; 20 (1): 28-37

  Abstract

  Pulmonary arterial hypertension (PAH) is associated with significant perioperative risk for major complications in children, including pulmonary hypertensive crisis and cardiac arrest. Uncertainty remains about the safety of ketamine anesthesia in this patient population.Retrospectively review the medical records of children with PAH to ascertain the nature and frequency of peri-procedural complications and to determine whether ketamine administration was associated with peri-procedural complications.Children with PAH (mean pulmonary artery pressure > or =25 mmHg and pulmonary vascular resistance index > or =3 Wood units) who underwent general anesthesia for procedures during a 6-year period (2002-2008) were enrolled. Details about the patient, PAH, procedure, anesthetic and postprocedural course were noted, including adverse events during or within 48 h of the procedure. Complication rates were reported per procedure. Association between ketamine and peri-procedural complications was tested.Sixty-eight children (median age 7.3 year, median weight 22 kg) underwent 192 procedures. Severity of PAH was mild (23%), moderate (37%), and severe (40%). Procedures undertaken were major surgery (n = 20), minor surgery (n = 27), cardiac catheterization (n = 128) and nonsurgical procedures (n = 17). Ketamine was administered during 149 procedures. Twenty minor and nine major complications were noted. Incidence of cardiac arrest was 0.78% for cardiac catheterization procedures, 10% for major surgical procedures and 1.6% for all procedures. There was no procedure-related mortality. Ketamine administration was not associated with increased complications.Ketamine appears to be a safe anesthetic option for children with PAH. We report rates for cardiopulmonary resuscitation and mortality that are more favorable than those previously reported.

  View details for DOI 10.1111/j.1460-9592.2009.03166.x

  View details for PubMedID 20078799

• Airway and ventilatory management ANESTHESIA FOR CONGENITAL HEART DISEASE Stayer, S. A., Hammer, G. B., Andropoulos, D. B., Stayer, S. A., Russell, Mossad, E. B. 2010: 338–55

  View details for DOI 10.1002/9781444314328.ch18

  View details for Web of Science ID 000288747800019

• Regional anesthesia and postoperative pain management ANESTHESIA FOR CONGENITAL HEART DISEASE Boltz, M., Hammer, G. B., Andropoulos, D. B., Andropoulos, D. B., Stayer, S. A., Russell, Mossad, E. B. 2010: 356–70

  View details for DOI 10.1002/9781444314328.ch19

  View details for Web of Science ID 000288747800020

• Airway responses to desflurane during maintenance of anesthesia and recovery in children with laryngeal mask airways. Pediatr Anesth Lerman J, Hammer GB, Verghese ST, Deutsch J 2010; 20: 495-505
• Population pharmacokinetic-pharmacodynamic modeling of the hypotensive effect of remifentanil in infants undergoing cranioplasty. Pediatr Anesth Standing JF, Hammer GB, Sam WJ, Drover DR 2010; 20: 7-18
• Pharmacokinetic-pharmacodynamic modeling of the hypotensive effect of remifentanil in infants undergoing cranioplasty PEDIATRIC ANESTHESIA Standing, J. F., Hammer, G. B., Sam, W. J., Drover, D. R. 2010; 20 (1): 7-18

  Abstract

  Although remifentanil has been used to induce hypotension during surgery in infants, no pharmacokinetic-pharmacodynamic (PKPD) model exists for its quantitative analysis. Our aim was to determine the quantitative relationship between whole blood remifentanil concentration and its hypotensive effect during surgery in infants.We studied seven infants (age 0.3-1 year) who underwent cranioplasty surgery and received remifentanil delivered by a computer-controlled infusion pump during the maintenance of anesthesia. Arterial blood samples to determine remifentanil concentration and mean arterial blood pressure (MAP) measurements were collected. A simultaneous PKPD mixed-effects model was built in NONMEM.A total of 77 remifentanil concentrations and 185 MAP measurements were collected. Remifentanil pharmacokinetics was described with a two-compartment model, parameter estimates were 2.99 l x min(-1) x 70 kg(-1) for clearance and 16.23 l x 70 kg(-1) for steady state volume of distribution. Mean baseline MAP was 69.7 mmHg and was decreased as per clinical requirements. A sigmoidal E(max) model driven by an effect compartment described the decrease in MAP, with an estimated concentration to decrease MAP by half (EC(50)) being 17.1 ng x ml(-1).Remifentanil is effective in causing hypotension. The final model predicts that a steady state remifentanil concentration of 14 ng.ml(-1) would typically achieve a 30% decrease in MAP.

  View details for DOI 10.1111/j.1460-9592.2009.03174.x

  View details for Web of Science ID 000273525800002

  View details for PubMedID 19825011

• Sedation and analgesia in the pediatric intensive care unit following laryngotracheal reconstruction PEDIATRIC ANESTHESIA Hammer, G. B. 2009; 19: 166-179

  Abstract

  Children undergoing laryngotracheal reconstruction (LTR) may remain electively intubated in the pediatric intensive care unit (PICU) for several days following surgery to facilitate wound healing. These patients require sedation and analgesia with or without neuromuscular blockade in order to prevent excessive head and neck movement with resultant tension on the tracheal anastomosis. Achieving this level of immobility features in caring for these children.The aims of this article are to describe a variety of commonly used sedation and analgesic agents and to provide guidance as to their optimal use following LTR.

  View details for DOI 10.1111/j.1460-9592.2009.03000.x

  View details for PubMedID 19572854

• Determination of the pharmacodynamic interaction of propofol and dexmedetomidine during esophagogastroduodenoscopy in children PEDIATRIC ANESTHESIA Hammer, G. B., Sam, W. J., Chen, M. I., Golianu, B., Drover, D. R. 2009; 19 (2): 138-144

  Abstract

  Propofol is a sedative-hypnotic drug commonly used to anesthetize children undergoing esophagogastroduodenoscopy (EGD). Dexmedetomidine is a highly selective alpha-2 adrenergic receptor agonist that has been utilized in combination with propofol to provide anesthesia. There is currently no information regarding the effect of intravenous dexmedetomidine on the propofol plasma concentration-response relationship during EGD in children. This study aimed to investigate the pharmacodynamic interaction of propofol and dexmedetomidine when used in combination for children undergoing EGD.A total of 24 children undergoing EGD, ages 3-10 years, were enrolled in this study. Twelve children received dexmedetomidine 1 microg x kg(-1) given over 10 min as well as a continuous infusion of propofol delivered by a computer-assisted target-controlled infusion (TCI) system with target plasma concentrations ranging from 2.8 to 4.0 microg x ml(-1) (DEX group). Another group of 12 children undergoing EGD also received propofol administered by TCI targeting comparable plasma concentrations without dexmedetomidine (control group). We used logistic regression to predict plasma propofol concentrations at which 50% of the patients exhibited minimal response to stimuli (EC50 for anesthesia).The EC50 +/- SE values in the control and DEX groups were 3.7 +/- 0.4 microg x ml(-1) and 3.5 +/- 0.2 microg x ml(-1), respectively. There was no significant shift in the propofol concentration-response curve in the presence of dexmedetomidine.The EC50 of propofol required to produce adequate anesthesia for EGD in children was unaffected by a concomitant infusion of dexmedetomidine 1 microg x kg(-1) given over 10 min.

  View details for DOI 10.1111/j.1460-9592.2008.02823.x

  View details for PubMedID 19207899

• Appropriate Endotracheal Tube Placement in Children: Don't Throw Away Your Stethoscopes Yet! ANESTHESIOLOGY Mariano, E. R., Ramamoorthy, C., Hammer, G. B. 2009; 110 (2): 433-434

  View details for Web of Science ID 000262907500038

  View details for PubMedID 19164968

• Population pharmacokinetics of remifentanil in infants and children undergoing cardiac surgery. BMC anesthesiology Sam, W. J., Hammer, G. B., Drover, D. R. 2009; 9: 5-?

  Abstract

  The aim of this study was to provide a model-based analysis of the pharmacokinetics of remifentanil in infants and children undergoing cardiac surgery with cardiopulmonary bypass (CPB).We studied nine patients aged 0.5 to 4 years who received a continuous remifentanil infusion via a computer-controlled infusion pump during cardiac surgery with mildly hypothermic CPB were studied. Arterial blood samples taken prior to, during and after CPB were analyzed for remifentanil concentrations using a validated gas-chromatographic mass-spectrophotometric assay. We used population mixed-effects modeling to characterize remifentanil pharmacokinetics. The final model was evaluated by its predictive performance.The pharmacokinetics of remifentanil was described by a 1-compartment model with adjustments for CPB. Population mean parameter estimates were 1.41 L for volume of distribution (V) and 0.244 L/min for clearance. V was increased during CPB and post-CPB to 2.41 times the pre-CPB value. The median prediction error and the median of individual median absolute prediction error were 2.44% and 21.6%, respectively.Remifentanil dosage adjustments are required during and after CPB due to marked changes in the V of the drug. Simulations indicate that a targeted blood concentration of 14 ng/mL is achieved and maintained in 50% of typical patients by administration of an initial dose of 18 mug remifentanil followed by an infusion of 3.7 mug/min before, during and post-CPB, supplemented with a bolus dose of 25 mug given at the start of CPB.

  View details for DOI 10.1186/1471-2253-9-5

  View details for PubMedID 19635151

• Sedation and Analgesia in the Pediatric Intensive Care Unit Following Laryngotracheal Reconstruction OTOLARYNGOLOGIC CLINICS OF NORTH AMERICA Hammer, G. B. 2008; 41 (5): 1023-?

  Abstract

  Deep levels of sedation and analgesia are needed in the majority of children who require prolonged tracheal intubation after laryngotracheal reconstruction (LTR). Drug doses may be determined most appropriately using validated scoring tools for sedation and analgesia; these scales continue to evolve and are used with increasing regularity in the pediatric intensive care unit (PICU). In this presentation, the validated scoring tools used to assess sedation and analgesia are reviewed, and specific agents used to manage sedation, analgesia, and neuromuscular blockade in the PICU after LTR are discussed.

  View details for DOI 10.1016/j.otc.2008.04.013

  View details for PubMedID 18775348

• The use of aprotinin in pediatric cardiac surgery: should we bid 'good riddance' or are we throwing out the baby with the bath water? PEDIATRIC ANESTHESIA Twite, M. D., Hammer, G. B. 2008; 18 (9): 809–11

  View details for DOI 10.1111/j.1460-9592.2008.02717.x

  View details for Web of Science ID 000257990900001

  View details for PubMedID 18768039

• Dexmedetomidine should not be used for infants and children during cardiac surgery JOURNAL OF CARDIOTHORACIC AND VASCULAR ANESTHESIA Hammer, G. B. 2008; 22 (1): 152-154

  View details for DOI 10.1053/j.jvca.2007.10.007

  View details for PubMedID 18249351

• Pharmacokinetics And Pharmacodynamics Of Fenoldopam Mesylate For Blood Pressure Control In Pediatric Patients. BMC anesthesiology Hammer, G. B., Verghese, S. T., Drover, D. R., Yaster, M., Tobin, J. R. 2008; 8: 6-?

  Abstract

  Fenoldopam mesylate, a selective dopamine1-receptor agonist, is used by intravenous infusion to treat hypertension in adults. Fenoldopam is not approved by the FDA for use in children; reports describing its use in pediatrics are limited. In a multi-institutional, placebo controlled, double-blind, multi-dose trial we determined the pharmacokinetic (PK) and pharmacodynamic (PD) characteristics and side-effect profile of fenoldopam in children.Seventy seven (77) children from 3 weeks to 12 years of age scheduled for surgery in which deliberate hypotension would be induced were enrolled. Patients were randomly assigned to one of five, blinded treatment groups (placebo or fenoldopam 0.05, 0.2, 0.8, or 3.2 mcg/kg/min iv) for a 30-minute interval after stabilization of anesthesia and placement of vascular catheters. Following the 30-minute blinded interval, investigators adjusted the fenoldopam dose to achieve a target mean arterial pressure in the open-label period until deliberate hypotension was no longer indicated (e.g., muscle-layer closure). Mean arterial pressure and heart rate were continuously monitored and were the primary endpoints.Seventy-six children completed the trial. Fenoldopam at doses of 0.8 and 3.2 mcg/kg/min significantly reduced blood pressure (p < 0.05) during the blinded interval, and doses of 1.0-1.2 mcg/kg/min resulted in continued control of blood pressure during the open-label interval. Doses greater than 1.2 mcg/kg/min during the open-label period resulted in increasing heart rate without additional reduction in blood pressure. Fenoldopam was well-tolerated; side effects occurred in a minority of patients. The PK/PD relationship of fenoldopam in children was determined.Fenoldopam is a rapid-acting, effective agent for intravenous control of blood pressure in children. The effective dose range is significantly higher in children undergoing anesthesia and surgery (0.8-1.2 mcg/kg/min) than as labeled for adults (0.05-0.3 mcg/kg/min). The PK and side-effect profiles for children and adults are similar.

  View details for DOI 10.1186/1471-2253-8-6

  View details for PubMedID 18837982

• The effects of dexmedetomidine on cardiac electrophysiology in children ANESTHESIA AND ANALGESIA Hammer, G. B., Drover, D. R., Cao, H., Jackson, E., Williams, G. D., Ramamoorthy, C., Van Hare, G. F., Niksch, A., Dubin, A. M. 2008; 106 (1): 79-83

  Abstract

  Dexmedetomidine (DEX) is an alpha2-adrenergic agonist that is approved by the Food and Drug Administration for short-term (<24 h) sedation in adults. It is not approved for use in children. Nevertheless, the use of DEX for sedation and anesthesia in infants and children appears to be increasing. There are some concerns regarding the hemodynamic effects of the drug, including bradycardia, hypertension, and hypotension. No data regarding the effects of DEX on the cardiac conduction system are available. We therefore aimed to characterize the effects of DEX on cardiac conduction in pediatric patients.Twelve children between the ages of 5 and 17 yr undergoing electrophysiology study and ablation of supraventricular accessory pathways had hemodynamic and cardiac electrophysiologic variables measured before and during administration of DEX (1 microg/kg IV over 10 min followed by a 10-min continuous infusion of 0.7 microg x kg(-1) x h(-1)).Heart rate decreased while arterial blood pressure increased significantly after DEX administration. Sinus node function was significantly affected, as evidenced by an increase in sinus cycle length and sinus node recovery time. Atrioventricular nodal function was also depressed, as evidenced by Wenckeback cycle length prolongation and prolongation of PR interval.DEX significantly depressed sinus and atrioventricular nodal function in pediatric patients. Heart rate decreased and arterial blood pressure increased during administration of DEX. The use of DEX may not be desirable during electrophysiology study and may be associated with adverse effects in patients at risk for bradycardia or atrioventricular nodal block.

  View details for DOI 10.1213/01.ane.0000297421.92857.4e

  View details for PubMedID 18165557

• Ketamine does not increase pulmonary vascular resistance in children with pulmonary hypertension undergoing sevoflurane anesthesia and spontaneous ventilation ANESTHESIA AND ANALGESIA Williams, G. D., Philip, B. M., Chu, L. F., Boltz, M. G., Kamra, K., Terwey, H., Hammer, G. B., Perry, S. B., Feinstein, J. A., Ramamoorthy, C. 2007; 105 (6): 1578-1584

  Abstract

  The use of ketamine in children with increased pulmonary vascular resistance is controversial. In this prospective, open label study, we evaluated the hemodynamic responses to ketamine in children with pulmonary hypertension (mean pulmonary artery pressure >25 mm Hg).Children aged 3 mo to 18 yr with pulmonary hypertension, who were scheduled for cardiac catheterization with general anesthesia, were studied. Patients were anesthetized with sevoflurane (1 minimum alveolar anesthetic concentration [MAC]) in air while breathing spontaneously via a facemask. After baseline catheterization measurements, sevoflurane was reduced (0.5 MAC) and ketamine (2 mg/kg IV over 5 min) was administered, followed by a ketamine infusion (10 microg x kg(-1) x min(-1)). Catheterization measurements were repeated at 5, 10, and 15 min after completion of ketamine load. Data at various time points were compared (ANOVA, P < 0.05).Fifteen patients (age 147, 108 mo; median, interquartile range) were studied. Diagnoses included idiopathic pulmonary arterial hypertension (5), congenital heart disease (9), and diaphragmatic hernia (1). At baseline, median (interquartile range) baseline pulmonary vascular resistance index was 11.3 (8.2) Wood units; 33% of patients had suprasystemic mean pulmonary artery pressures. Heart rate (99, 94 bpm; P = 0.016) and Pao2 (95, 104 mm Hg; P = 007) changed after ketamine administration (baseline, 15 min after ketamine; P value). There were no significant differences in mean systemic arterial blood pressure, mean pulmonary artery pressure, systemic or pulmonary vascular resistance index, cardiac index, arterial pH, or Paco2.In the presence of sevoflurane, ketamine did not increase pulmonary vascular resistance in spontaneously breathing children with severe pulmonary hypertension.

  View details for DOI 10.1213/01.ane.0000287656.29064.89

  View details for PubMedID 18042853

• Use of recombinant activated factor VII in children PEDIATRIC ANESTHESIA Hammer, G. B., Williams, G. D. 2007; 17 (12): 1123-1125

  View details for DOI 10.1111/j.1460-9592.2007.02344.x

  View details for Web of Science ID 000250648300001

  View details for PubMedID 17986029

• The use of dexmedetomidine during laryngoscopy, bronchoscopy, and tracheal extubation following tracheal reconstruction PEDIATRIC ANESTHESIA Seybold, J. L., Ramamurthi, R. J., Hammer, G. B. 2007; 17 (12): 1212-1214

  Abstract

  We report the use of dexmedetomidine for laryngoscopy, rigid bronchoscopy, and tracheal extubation in the operating room in two children who had undergone tracheal reconstruction 1 week previously. Dexmedetomidine in combination with propofol provided appropriately deep anesthesia during these brief but stimulating procedures without cardiovascular or respiratory depression.

  View details for DOI 10.1111/j.1460-9592.2007.02346.x

  View details for PubMedID 17986042

• An alternative airway adaptor for single-lung ventilation in infants ANESTHESIA AND ANALGESIA Hammer, G. B. 2007; 105 (3): 892–93

  View details for DOI 10.1213/01.ane.0000271903.60290.cf

  View details for Web of Science ID 000248924400081

  View details for PubMedID 17717276

• Opioid analgesia in neonates following cardiac surgery. Seminars in cardiothoracic and vascular anesthesia Hammer, G. B., Golianu, B. 2007; 11 (1): 47-58

  Abstract

  Pain in the newborn is complex, involving a variety of receptors and mechanisms within the developing nervous system. When pain is generated, a series of sequential neurobiologic changes occur within the central nervous system. If pain is prolonged or repetitive, the developing nervous system could be permanently modified, with altered processing at spinal and supraspinal levels. In addition, pain is associated with a number of adverse physiologic responses that include alterations in circulatory (tachycardia, hypertension, vasoconstriction), metabolic (increased catabolism), immunologic (impaired immune response), and hemostatic (platelet activation) systems. This "stress response" associated with cardiac surgery in neonates could be profound and is associated with increased morbidity and mortality. Neonates undergoing cardiac operations are exposed to extensive tissue damage related to surgery and additional painful stimulation related to endotracheal and thoracostomy tubes that may remain in place for variable periods of time following surgery. In addition, postoperatively neonates endure repeated procedural pain from suctioning of endotracheal tubes, placement of vascular catheters, and manipulation of wounds (eg, sternal closure) and dressings. The treatment and/or prevention of pain are widely considered necessary for humanitarian and physiologic reasons. Improved clinical and developmental outcomes underscore the importance of providing adequate analgesia for newborns who undergo major surgery, mechanical ventilation, and related procedures in the intensive care unit. This article reviews published information regarding opioid administration and associated issues of tolerance and abstinence syndromes (withdrawal) in neonates with an emphasis on those having undergone cardiac surgery.

  View details for PubMedID 17484173

• Sevoflurane and emergence delirium Clin Ped Anesth Hammer GB 2007; 13: 38-41
• Total intravenous anesthesia in infants and children. Clin Ped Anesth Hammer GB 2007; 13: 49-51
• Modified and conventional ultrafiltration during pediatric cardiac surgery: Clinical outcomes compared JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Williams, G. D., Ramamoorthy, C., Chu, L., Hammer, G. B., Kamra, K., Boltz, M. G., Pentcheva, K., McCarthy, J. P., Reddy, V. M. 2006; 132 (6): 1291-1298

  Abstract

  This prospective study compared clinical outcomes after heart surgery between three groups of infants with congenital heart disease. One group received dilutional conventional ultrafiltration (group D), another received modified ultrafiltration (group M), and a third group received both dilutional conventional and modified ultrafiltration (group B). We hypothesized that group B patients would have the best clinical outcome.Children younger than 1 year undergoing heart surgery for biventricular repair by the same surgeon were randomly allocated to one of the three study groups. Patient management was standardized, and intensive care staff were blinded to group allocation. Primary outcome measure was duration of postoperative mechanical ventilation. Other outcome measures recorded included total blood products transfused, duration of chest tube in situ, chest tube output, and stays in intensive care and in the hospital.Sixty infants completed study protocol. Mean age and weight were as follows: group D (n = 19), 61 days, 4.3 kg; group M (n = 20), 64 days, 4.5 kg; and group B (n = 21), 86 days, 4.4 kg. Preoperative and intraoperative characteristics were similar between groups. Ultrafiltrate volumes obtained were 196 +/- 93 mL/kg in group D, 105 +/- 33 mL/kg in group M, and 261 +/- 113 mL/kg in group B. There were no significant differences between groups for any outcome variable. Technical difficulties prevented completion of modified ultrafiltration in 2 of 41 infants.There was no clinical advantage in combining conventional and modified ultrafiltration. Because clinical outcomes were similar across groups, relative risks of the ultrafiltration strategies may influence choice.

  View details for DOI 10.1016/j.jtcvs.2006.05.059

  View details for PubMedID 17140945

• Lung isolation in a child with unilateral necrotizing Clostridium perfringens pneumonia CRITICAL CARE MEDICINE Brady, K. M., Harris, Z. L., Hammer, G. B., Berkowitz, I. D., Easley, R. B. 2005; 33 (11): 2676-2680

  Abstract

  To describe lung isolation and the selective application of continuous positive airway pressure using an endobronchial blocker in a patient with sickle cell disease and unilateral necrotizing Clostridium perfringens pneumonia.Case report.Pediatric intensive care unit.A 12-yr-old male with sickle cell disease developed persistent necrotizing pneumonia of the left lung following exchange transfusion for acute chest syndrome and hyper-hemolytic syndrome.An endobronchial blocker was placed into the left main stem bronchus for lung isolation and application of continuous positive airway pressure to the left lung for 48 hrs.After 14 days of persistent atelectasis of the left lung despite thorascopic decortication and multiple bronchoscopies, our patient had substantial lung aeration within 48 hrs of continuous positive airway pressure applied via the endobronchial blocker. Lung resection was avoided and the patient was successfully extubated 2 days after removal of the blocker.This case report demonstrates a therapeutic application of prolonged lung isolation and differential ventilation in a patient with an airway too small for commercially available double-lumen endotracheal tubes. The apparent success of this intervention suggests the feasibility of selective ventilation in pediatric patients and highlights a novel application of the bronchial blocker.

  View details for DOI 10.1097/01.CCM.0000186776.40271.6A

  View details for Web of Science ID 000234423500033

  View details for PubMedID 16276197

• A comparison of three methods for estimating appropriate tracheal tube depth in children PEDIATRIC ANESTHESIA Mariano, E. R., Ramamoorthy, C., Chu, L. F., Chen, M., Hammer, G. B. 2005; 15 (10): 846-851

  Abstract

  Estimating appropriate tracheal tube (TT) depth following tracheal intubation in infants and children presents a challenge to anesthesia practitioners. We evaluated three methods commonly used by anesthesiologists to determine which one most reliably results in appropriate positioning.After IRB approval, 60 infants and children scheduled for fluoroscopic procedures requiring general anesthesia were enrolled. Patients were randomly assigned to one of three groups: (1) deliberate mainstem intubation with subsequent withdrawal of the TT 2 cm above the carina ('mainstem' method); (2) alignment of the double black line marker near the TT tip at the vocal cords ('marker' method); or (3) placement of the TT at a depth determined by the formula: TT depth (cm) = 3 x TT size (mmID) ('formula' method). TT tip position was determined to be 'appropriate' if located between the sternoclavicular junction (SCJ) and 0.5 cm above the carina as determined by fluoroscopy. Risk ratios were calculated, and data were analysed by the chi-square test accepting statistical significance at P < 0.05.The mainstem method was associated with the highest rate of appropriate TT placement (73%) compared with both the marker method (53%, P = 0.03, RR = 1.56) and the formula method (42%, P = 0.006, RR = 2.016). There was no difference between the marker and formula methods overall (P = 0.2, RR = 1.27). Analysis of age-stratified data demonstrated higher success with the marker method compared with the formula method for patients 3-12 months (P = 0.0056, RR = 4.0).Deliberate mainstem intubation most reliably results in appropriate TT depth in infants and children.

  View details for DOI 10.1111/j.1460-9592.2005.01577.x

  View details for Web of Science ID 000232471900005

  View details for PubMedID 16176312

• Prolonged infusion of dexmedetomidine for sedation following tracheal resection PEDIATRIC ANESTHESIA Hammer, G. B., Philip, B. M., Schroeder, A. R., Rosen, F. S., Koltai, P. J. 2005; 15 (7): 616-620

  Abstract

  Dexmedetomidine is a centrally acting alpha-2 adrenergic agonist that is currently approved by the US Food and Drug Administration for short-term use (< or = 24 h) to provide sedation in adults in the ICU. This drug has been shown to be efficacious in adult medical and surgical patients in providing sedation, anxiolysis, and analgesia. Dexmedetomidine has been associated with rapid onset and offset, hemodynamic stability, and a natural, sleep-like state in mechanically ventilated adults. To date, there are few publications of the use of this drug in children, and prolonged infusion has not been described. We report our use of dexmedetomidine in a child during a 4-day period of mechanical ventilation following tracheal reconstruction for subglottic stenosis.

  View details for DOI 10.1111/j.1460-9592.2005.01656.x

  View details for PubMedID 15960649

• Postoperative analgesia after spinal blockade in infants and children undergoing cardiac surgery ANESTHESIA AND ANALGESIA Hammer, G. B., Ramamoorthy, C., Cao, H., Williams, G. D., Boltz, M. G., Kamra, K., Drover, D. R. 2005; 100 (5): 1283-1288

  Abstract

  The aim of this prospective, randomized, controlled clinical trial was to define the opioid analgesic requirement after a remifentanil (REMI)-based anesthetic with spinal anesthetic blockade (SAB+REMI) or without (REMI) spinal blockade for open-heart surgery in children. We enrolled 45 patients who were candidates for tracheal extubation in the operating room after cardiac surgery. Exclusion criteria included age <3 mo and >6 yr, pulmonary hypertension, congestive heart failure, contraindication to SAB, and failure to obtain informed consent. All patients had an inhaled induction with sevoflurane and maintenance of anesthesia with REMI and isoflurane (0.3% end-tidal). In addition, patients assigned to the SAB+REMI group received SAB with tetracaine (0.5-2.0 mg/kg) and morphine (7 mug/kg). After tracheal extubation in the operating room, patients received fentanyl 0.3 mug/kg IV every 10 min by patient-controlled analgesia for pain score = 4. Pain scores and fentanyl doses were recorded every hour for 24 h or until the patient was ready for discharge from the intensive care unit. Patients in the SAB+REMI group had significantly lower pain scores (P = 0.046 for the first 8 h; P =0.05 for 24 h) and received less IV fentanyl (P = 0.003 for the first 8 h; P = 0.004 for 24 h) than those in the REMI group. There were no intergroup differences in adverse effects, including hypotension, bradycardia, highest PaCO(2), lowest pH, episodes of oxygen desaturation, pruritus, and vomiting.

  View details for DOI 10.1213/01.ANE.0000148698.84881.10

  View details for PubMedID 15845670

• Pediatric thoracic anesthesia. Current opinion in anaesthesiology Golianu, B., Hammer, G. B. 2005; 18 (1): 5-11

  Abstract

  Surgical interventions, including video-assisted thoracoscopic surgeries, are increasingly being performed in the neonatal and pediatric populations. Thoracic anesthesia in infants and children poses special challenges for the anesthesiologist. These include assessment of the patient's clinical condition, obtaining and maintaining single lung ventilation, and maintaining adequate ventilation and oxygenation while the surgery is in progress.This review will outline the anesthetic management of infants and children undergoing thoracic surgery, including preoperative assessment, and anesthetic induction and maintenance. The physiology and methods of single lung ventilation will be reviewed, including the use of bronchial blockers, Univent tubes and double-lumen tubes. Special considerations for video-assisted thoracoscopic surgery, pectus repair and mediastinal masses will be discussed.These techniques will provide the anesthesiologist with a number of strategies for assessing the pediatric thoracic patient and for managing pediatric single lung ventilation.

  View details for PubMedID 16534311

• Pediatric thoracic anesthesia CURRENT OPINION IN ANESTHESIOLOGY Golianu, B., Hammer, G. B. 2005; 18 (1): 5-11

  Abstract

  Surgical interventions, including video-assisted thoracoscopic surgeries, are increasingly being performed in the neonatal and pediatric populations. Thoracic anesthesia in infants and children poses special challenges for the anesthesiologist. These include assessment of the patient's clinical condition, obtaining and maintaining single lung ventilation, and maintaining adequate ventilation and oxygenation while the surgery is in progress.This review will outline the anesthetic management of infants and children undergoing thoracic surgery, including preoperative assessment, and anesthetic induction and maintenance. The physiology and methods of single lung ventilation will be reviewed, including the use of bronchial blockers, Univent tubes and double-lumen tubes. Special considerations for video-assisted thoracoscopic surgery, pectus repair and mediastinal masses will be discussed.These techniques will provide the anesthesiologist with a number of strategies for assessing the pediatric thoracic patient and for managing pediatric single lung ventilation.

  View details for Web of Science ID 000209516600002

• Pain management for pediatric thoracic surgery CURRENT OPINION IN ANESTHESIOLOGY Golianu, B., Hammer, G. B. 2005; 18 (1): 13-21

  Abstract

  Pain management after thoracic surgery in children presents the challenge of providing adequate analgesia without excessive sedation, and maintaining adequate respiratory function in the face of compromise resulting from existing pathology, surgical trauma, single-lung ventilation and postoperative ventilation-perfusion abnormalities. In the pediatric population, pain assessment and reporting present additional challenges. The number and complexity of surgical procedures, including video-assisted thoracoscopic procedures, is increasing in the pediatric population. There is a need to explore pain management for these types of patients.There are effective and safe strategies whereby analgesia can be provided to this pediatric population. This review will outline the progress that has been made in this field, including the use of regional techniques. The routine use of caudal catheters in neonates and infants for thoracic surgical procedures and the use of electrical guidance of epidural catheters, the 'Tsui' technique, are reviewed.These techniques, applied within a comprehensive pain management strategy, can be extremely beneficial in the care of the pediatric thoracic patient.

  View details for Web of Science ID 000209516600003

• Pain management for pediatric thoracic surgery. Current opinion in anaesthesiology Golianu, B., Hammer, G. B. 2005; 18 (1): 13-21

  Abstract

  Pain management after thoracic surgery in children presents the challenge of providing adequate analgesia without excessive sedation, and maintaining adequate respiratory function in the face of compromise resulting from existing pathology, surgical trauma, single-lung ventilation and postoperative ventilation-perfusion abnormalities. In the pediatric population, pain assessment and reporting present additional challenges. The number and complexity of surgical procedures, including video-assisted thoracoscopic procedures, is increasing in the pediatric population. There is a need to explore pain management for these types of patients.There are effective and safe strategies whereby analgesia can be provided to this pediatric population. This review will outline the progress that has been made in this field, including the use of regional techniques. The routine use of caudal catheters in neonates and infants for thoracic surgical procedures and the use of electrical guidance of epidural catheters, the 'Tsui' technique, are reviewed.These techniques, applied within a comprehensive pain management strategy, can be extremely beneficial in the care of the pediatric thoracic patient.

  View details for PubMedID 16534312

• Determination of the pharmacodynamic interaction of propofol and remifentanil during esophagogastroduodenoscopy in children ANESTHESIOLOGY Drover, D. R., Litalien, C., Wellis, V., Shafer, S. L., Hammer, G. B. 2004; 100 (6): 1382-1386

  Abstract

  Propofol is commonly used to anesthetize children undergoing esophagogastroduodenoscopy. Opioids are often used in combination with propofol to provide total intravenous anesthesia. Because both propofol and remifentanil are associated with rapid onset and offset, the combination of these two drugs may be particularly useful for procedures of short duration, including esophagogastroduodenoscopy. The authors previously demonstrated that the median effective concentration (C50) of propofol during esophagogastroduodenoscopy in children is 3.55 microg/ml. The purpose of this study was to describe the pharmacodynamic interaction of remifentanil and propofol when used in combination for esophagogastroduodenoscopy in pediatric patients.The authors studied 32 children aged between 3 and 10 yr who were scheduled to undergo esophagogastroduodenoscopy. Propofol was administered via a target-controlled infusion system using the STANPUMP software based on a pediatric pharmacokinetic model. Remifentanil was administered as a constant rate infusion of 25, 50, and 100 ng.kg(-1).min(-1) to each of three study groups, respectively. A sigmoid Emax model was developed to describe the interaction of remifentanil and propofol.There was a positive interaction between remifentanil and propofol when used in combination. The concentration of propofol alone associated with 50% probability of no response was 3.7 microg/ml (SE, 0.4 microg/ml), and this was decreased to 2.8 microg/ml (SE, 0.1 microg/ml) when used in combination with remifentanil.A remifentanil infusion of 25 ng.kg(-1).min(-1) reduces the concentration of propofol required for adequate anesthesia for esophagogastroduodenoscopy from 3.7 to 2.8 microg/ml. Increasing the remifentanil infusion yields minimal additional decrease in propofol concentration and may increase the risk of side effects.

  View details for Web of Science ID 000221551300007

  View details for PubMedID 15166555

• Anaesthetic management for the child with a mediastinal mass 4th International Symposium on the Pediatric Airway Hammer, G. B. WILEY-BLACKWELL PUBLISHING, INC. 2004: 95–97

  Abstract

  Administering anaesthesia to a child with an anterior mediastinal mass may lead to respiratory or circulatory collapse, even in those without symptoms. Institutions should have algorithms to manage children with mediastinal masses. Preoperative evaluations should include computed tomography, echocardiography and flow-volume studies. Anaesthesia may be induced with inhalation agents and maintained with spontaneous respiration via facemask or laryngeal mask airway. Alternatively, positive-pressure ventilation may be used, including tracheal intubation without muscle relaxants. Rigid bronchoscopy may be life-saving in the event of tracheal or bronchial collapse under anaesthesia.

  View details for Web of Science ID 000222055000014

• Single-lung ventilation in infants and children Hammer, G. B. BLACKWELL PUBLISHING LTD. 2004: 98–102

  Abstract

  During the past decade, the use of video-assisted thoracoscopic surgery (VATS) has dramatically increased in children as well as adults. Although VATS can be performed while both lungs are being ventilated, single-lung ventilation (SLV) is desirable during VATS. In addition, anaesthesiologists are performing (and paediatric surgeons are requesting) SLV more frequently for open thoracotomies in infants and children.

  View details for PubMedID 14717881

• Anaesthetic management for the child with a mediastinal mass. Paediatric anaesthesia Hammer, G. B. 2004; 14 (1): 95–97

  Abstract

  Administering anaesthesia to a child with an anterior mediastinal mass may lead to respiratory or circulatory collapse, even in those without symptoms. Institutions should have algorithms to manage children with mediastinal masses. Preoperative evaluations should include computed tomography, echocardiography and flow-volume studies. Anaesthesia may be induced with inhalation agents and maintained with spontaneous respiration via facemask or laryngeal mask airway. Alternatively, positive-pressure ventilation may be used, including tracheal intubation without muscle relaxants. Rigid bronchoscopy may be life-saving in the event of tracheal or bronchial collapse under anaesthesia.

  View details for PubMedID 14717880

• Single-lung ventilation in infants and children 4th International Symposium on the Pediatric Airway Hammer, G. B. WILEY-BLACKWELL PUBLISHING, INC. 2004: 98–102

  Abstract

  During the past decade, the use of video-assisted thoracoscopic surgery (VATS) has dramatically increased in children as well as adults. Although VATS can be performed while both lungs are being ventilated, single-lung ventilation (SLV) is desirable during VATS. In addition, anaesthesiologists are performing (and paediatric surgeons are requesting) SLV more frequently for open thoracotomies in infants and children.

  View details for Web of Science ID 000222055000015

• Differential lung ventilation in infants and children with pulmonary hyperinflation PAEDIATRIC ANAESTHESIA Hammer, G. B. 2003; 13 (5): 373–74

  View details for DOI 10.1046/j.1460-9592.2003.01086.x

  View details for Web of Science ID 000183368800001

  View details for PubMedID 12791108

• Transesophageal echocardiography-guided transventricular balloon dilation of congenital critical aortic stenosis in the neonate and young infant JOURNAL OF CARDIOTHORACIC AND VASCULAR ANESTHESIA Hussain, A., al Faraidi, Y., Abdulhamed, J., Bacha, E. A., Hammer, G. B., Feinstein, J. B. 2002; 16 (6): 766-772

  View details for DOI 10.1053/jcan.2002.128435

  View details for Web of Science ID 000179855800019

  View details for PubMedID 12486662

• Pro: Regional anesthesia is an important component of the anesthetic technique for pediatric patients undergoing cardiac surgical procedures JOURNAL OF CARDIOTHORACIC AND VASCULAR ANESTHESIA Rosen, D. A., Rosen, K. R., Hammer, G. B. 2002; 16 (3): 374-378

  View details for DOI 10.1053/jcan.2002.124152

  View details for Web of Science ID 000176417200022

  View details for PubMedID 12073215

• Paradoxical vocal cord motion in a child presenting with cyanosis and respiratory failure. Pediatric critical care medicine Falco, D. A., Hammer, G. B., Conrad, C., Messner, A. H. 2002; 3 (2): 185-186

  View details for PubMedID 12780992

• Pediatric thoracic anesthesia. Anesthesiology clinics of North America Hammer, G. B. 2002; 20 (1): 153-180

  Abstract

  The anesthesiologist caring for infants and children undergoing thoracic surgery faces many challenges. An understanding of the primary underlying lesion as well as associated anomalies that may impact perioperative management is paramount. A working knowledge of respiratory physiology and anatomy in infants and children is required for the planning and execution of appropriate intraoperative care. Familiarity with a variety of techniques for SLV suited to the patient's size will allow maximal surgical exposure while minimizing trauma to the lungs and airways. Finally, use of regional anesthetic techniques, including epidural anesthesia and analgesia, facilitates optimal postoperative pain control and pulmonary function.

  View details for PubMedID 11892503

• Single lung ventilation in children using a new paediatric bronchial blocker PAEDIATRIC ANAESTHESIA Hammer, G. B., Harrison, T. K., Vricella, L. A., Black, M. D., Krane, E. J. 2002; 12 (1): 69-72

  Abstract

  As video-assisted thoracoscopic surgery has become more common in paediatric patients, the use of single lung ventilation in children has also increased. Single lung ventilation in young children is performed by either advancing a tracheal tube into the mainstem bronchus opposite the side of surgery or by positioning a bronchial blocker into the mainstem bronchus on the operative side. Techniques for placing a variety of bronchial blockers outside the tracheal tube have been described. We describe a technique for placement of a new bronchial blocker through an indwelling tracheal tube using a multiport adaptor and a fibreoptic bronchoscope.

  View details for PubMedID 11849579

• Anesthesia for outpatient repair of patent ductus arteriosus JOURNAL OF CARDIOTHORACIC AND VASCULAR ANESTHESIA Uezono, S., Hammer, G. B., Wellis, V., Boltz, M. G., Pike, N. A., Black, M. D. 2001; 15 (6): 750-752

  View details for DOI 10.1053/jcan.2001.28322

  View details for PubMedID 11748526

• Selective bronchial blockade in small infants ANESTHESIA AND ANALGESIA Hammer, G. B. 2001; 93 (6): 1624–25

  View details for DOI 10.1097/00000539-200112000-00067

  View details for Web of Science ID 000172364000056

  View details for PubMedID 11726460

• Pediatric thoracic anesthesia and high-frequency jet ventilation - In Response ANESTHESIA AND ANALGESIA Hammer, G. B. 2001; 93 (5): 1362

  View details for DOI 10.1097/00000539-200111000-00071

  View details for Web of Science ID 000171820500065

• A technique for maintenance of airway access in infants with a difficult airway following tracheal extubation PAEDIATRIC ANAESTHESIA Hammer, G. B., Funck, N., Rosenthal, D. N., Feinstein, J. A. 2001; 11 (5): 622-625

  Abstract

  Tracheal extubation of patients with a difficult airway represents a challenge to anaesthesiologists and intensive care physicians. While a variety of techniques designed to maintain access to the airway in case of the need for tracheal reintubation have been described in adults, no reports have been published in infants and young children. We describe an approach to this issue in a young child with severe micrognathia.

  View details for PubMedID 11696131

• Determination of the median effective concentration (EC50) of propofol during oesophagogastroduodenoscopy in children PAEDIATRIC ANAESTHESIA Hammer, G. B., Litalien, C., Wellis, V., Drover, D. R. 2001; 11 (5): 549-553

  Abstract

  Propofol is commonly used to provide anaesthesia for children undergoing oesophagogastroduodenoscopy (OGD). Despite this, the plasma concentration-response relationships for propofol used in this setting have not been established.In order to determine the EC50 of propofol during OGD, we studied 12 children aged 3-10 years. No premedication was given. Propofol was administered via a target-controlled infusion system using the STANPUMP software based on a paediatric pharmacokinetic model. The 'up-and-down' method described by Dixon was used to determine the EC50. Accordingly, the target plasma propofol concentration for each patient, beginning with the second subject, was determined by the response of the previous patient. A patient was considered a 'responder' if there was minimal movement and the heart rate (HR) and blood pressure (BP) remained < or = 120% of baseline during the procedure. Patients who moved excessively, i.e. requiring more than gentle restraint, or who manifest HR and BP >120% of baseline, were considered 'nonresponders'.The EC50 of propofol during OGD was 3.55 microg.ml(-1) in this study.The plasma propofol concentration associated with adequate anaesthesia for OGD in 50% of unpremedicated children is 3.55 microg.ml(-1). This concentration is higher than that required for OGD in adult patients.

  View details for PubMedID 11696118

• Pediatric thoracic anesthesia ANESTHESIA AND ANALGESIA Hammer, G. B. 2001; 92 (6): 1449-1464

  View details for PubMedID 11375825

• Anaesthesia for liver transplantation in children PAEDIATRIC ANAESTHESIA Hammer, G. B., Krane, E. J. 2001; 11 (1): 3-18

  View details for PubMedID 11123726

• A retrospective examination of regional plus general anesthesia in children undergoing open heart surgery ANESTHESIA AND ANALGESIA Hammer, G. B., Ngo, K., Macario, A. 2000; 90 (5): 1020-1024

  Abstract

  The use of regional anesthesia in combination with general anesthesia for children undergoing cardiac surgery is receiving increasing attention from clinicians. The addition of regional anesthesia may improve clinical outcomes and decrease costs as a result of the reduced need for postoperative mechanical ventilation. The goal of this retrospective chart review was to evaluate whether spinal anesthesia (SAB) or epidural anesthesia (EPID) in combination with general anesthesia was associated with circulatory stability, satisfactory postoperative sedation/analgesia, and a low incidence of adverse effects. The medical records of 50 consecutive children having open heart surgery with SAB or EPID and general anesthesia between September 1996 and December 1997 were reviewed. We found no significant differences in the incidence of clinically significant changes in vital signs, oxygen desaturation, hypercarbia, or vomiting. Patients in the SAB group received significantly more sedative/analgesic interventions than those in the EPID group.

  View details for PubMedID 10781446

• Methods for single-lung ventilation in pediatric patients ANESTHESIA AND ANALGESIA Hammer, G. B., Fitzmaurice, B. G., Brodsky, J. B. 1999; 89 (6): 1426-1429

  View details for PubMedID 10589621

• Determination of the median effective concentration (EC50) of propofol during esophagogastroduodenoscopy (EGD) in children Hammer, G. B., Litalien, C., Wellis, V., Drover, D., Garcia, M. LIPPINCOTT WILLIAMS & WILKINS. 1999: U493–U493

  View details for Web of Science ID 000082480601268

• Spinal vs. epidural anesthesia and analgesia in children undergoing open heart surgery Hammer, G. B., Ngo, K., Macario, A., Boltz, M. G., Hill, L. LIPPINCOTT WILLIAMS & WILKINS. 1999: U497–U497

  View details for Web of Science ID 000082480601285

• Determination of the EC50 of propofol combined with remifentanil during EGD in children Hammer, G. B., Litalien, C., Wellis, V., Drover, D., Garcia, M. LIPPINCOTT WILLIAMS & WILKINS. 1999: U492–U492

  View details for Web of Science ID 000082480601263

• Tracheal intubation in a child with trismus pseudocamptodactyly (Hecht) syndrome JOURNAL OF CLINICAL ANESTHESIA Seavello, J., Hammer, G. B. 1999; 11 (3): 254-256

  Abstract

  Tracheal intubation of a child with trismus pseudocamptodactyly (Hecht) syndrome is described. This disorder is characterized by progressive trismus and the need for repeated surgeries. Children intubated orally on a prior occasion may require an alternative approach subsequently due to progressive inability to open the mouth. An antegrade fiberoptic-guided nasotracheal technique initially was chosen due to extremely limited mouth opening. After this approach was unsuccessful, a retrograde guidewire-assisted fiberoptic intubation was performed. The manifestations of Hecht syndrome, as well as both techniques for tracheal intubation employed, are reviewed.

  View details for PubMedID 10434225

• Regional anesthesia for pediatric cardiac surgery JOURNAL OF CARDIOTHORACIC AND VASCULAR ANESTHESIA Hammer, G. B. 1999; 13 (2): 210-213

  View details for PubMedID 10230960

• A smaller double-lumen tube for older children JOURNAL OF CLINICAL ANESTHESIA Fitzmaurice, B. G., Zuckerman, K., Brodsky, J. B., Hammer, G. B. 1999; 11 (1): 79

  View details for Web of Science ID 000079813800016

  View details for PubMedID 10396725

• Post-transplant lymphoproliferative disease may present with severe airway obstruction ANESTHESIOLOGY Hammer, G. B., Cao, S., Boltz, M. G., Messner, A. 1998; 89 (1): 263-265

  View details for PubMedID 9667319

• The Univent tube for single-lung ventilation in paediatric patients PAEDIATRIC ANAESTHESIA Hammer, G. B., Brodsky, J. B., Redpath, J. H., Cannon, W. B. 1998; 8 (1): 55-57

  Abstract

  A Univent bronchial blocker tube was used in a ten-year-old patient undergoing videothoracoscopy. Paediatric Univent tubes offer an alternative to balloon-tipped catheters for providing single-lung ventilation (SLV) in children too small for adult size double-lumen tubes.

  View details for PubMedID 9483599

• Bladder augmentation can be problematic with renal failure and transplantation PEDIATRIC NEPHROLOGY Alfrey, E. J., Salvatierra, O., Tanney, D. C., Mak, R., Scandling, J. D., Dafoe, D. C., Hammer, G. B., Orlandi, P. D., Page, L., Conley, S. B. 1997; 11 (6): 672-675

  Abstract

  Ten consecutive patients with failure of urinary bladder augmentation (UBA) performed either prior to or after reaching end-stage renal disease (ESRD) were studied. Seven patients developed increased hydroureteronephrosis, infectious complications, and advanced to ESRD after UBA. The mean time to development of ESRD in patients who had UBA performed with moderate chronic renal failure (CRF) was 1.8 years. The UBAs in all seven patients were taken down prior to transplantation. Subsequently, five of these UBA-takedown patients have received kidney grafts and all have stable, good renal function. Three patients had their UBA performed after they reached ESRD, in preparation for renal transplantation. All three of these patients experienced recurrent urosepsis following transplantation, resulting in death in one patient and loss of graft in another. The third patient will undergo takedown of the UBA. This study suggests that UBA may possibly not be the best option for patients with moderate CRF and those awaiting transplantation.

  View details for PubMedID 9438639

• Failure to separate and isolate the lungs with an endotracheal tube positioned in the bronchus ANESTHESIA AND ANALGESIA Lammers, C. R., Hammer, G. B., Brodsky, J. B., Cannon, W. B. 1997; 85 (4): 946–47

  View details for DOI 10.1097/00000539-199710000-00048

  View details for Web of Science ID A1997XY23200048

  View details for PubMedID 9322490

• Superior outcomes in pediatric renal transplantation 68th Annual Session of the Pacific-Coast-Surgical-Association Salvatierra, O., Alfrey, E., Tanney, D. C., Mak, R., Hammer, G. B., Krane, E. J., So, S. K., Lemley, K., Orlandi, P. D., Conley, S. B. AMER MEDICAL ASSOC. 1997: 842–47

  Abstract

  Nationally, results of renal transplantation in children, particularly in small children, are inferior to those obtained in adults.To determine factors important for success in renal transplantation in children.Results of 108 consecutive renal transplantations performed in patients aged 7 months to 18 years were reviewed and compared with those reported by the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS), the national registry.One-, 2-, and 3-year graft survival rates (+/-SE) were 99% +/- 1%, 95% +/- 3%, and 93% +/- 4%, respectively, for living donor grafts and 97% +/- 3%, 92% +/- 6%, and 92% +/- 6%, respectively, for cadaver grafts. Incidence of acute rejection was half that reported by NAPRTCS. There were no graft losses for technical reasons (19% in NAPRTCS). Twelve percent of patients were younger than 2 years (6% in NAPRTCS); 17% were 2 to 5 years old (16% in NAPRTCS). Most small children received an adult-sized kidney. Ninety-three percent of recipients weighing 15 kg or less received postoperative mechanical ventilation assistance to optimize fluid resuscitation and perfusion of adult-sized kidneys. Structural abnormalities of the urinary tract were present in 53.7% of the patients (48.5% in NAPRTCS; adults, 5.3%). Nephroureterectomy was required in 38 children; in 27 (71%) of them, it was performed at the time of transplant surgery.Excellent results can be obtained in pediatric renal transplantation by strict adherence to surgical detail, tight immunosuppressive management, aggressive fluid management in the small child, and careful integration of urologic and transplant surgery.

  View details for PubMedID 9267267

• Factors affecting survival after orthotopic liver transplantation in infants TRANSPLANTATION Cacciarelli, T. V., Esquivel, C. O., Moore, D. H., Cox, K. L., Berquist, W. E., Concepcion, W., Hammer, G. B., So, S. K. 1997; 64 (2): 242-248

  Abstract

  The technical and medical management of small infants requiring orthotopic liver transplantation remains a challenge. The present study examined 117 orthotopic liver transplantations performed in 101 infants from <1 to 23 months of age between March 1988 and February 1995 to determine factors that influence patient and graft outcome. Factors analyzed included etiology of liver disease, recipient and donor age and weight, United Network for Organ Sharing (UNOS) status, retransplantation, ABO-compatibility, full-size (FS) versus reduced-size grafts, vascular thrombosis (VT), including hepatic artery and portal vein (PVT), and the presence of lymphoproliferative disease (LPD). UNOS status 1, fulminant hepatic failure, and the development of Epstein-Barr virus-associated LPD were each associated with 10-20% lower patient and graft survival rates. Of 101 infants, 11 (11%) developed LPD with an associated 36% mortality. VT occurred in 10 (9 hepatic artery and 1 portal vein) of 117 orthotopic liver transplantations (9%), all less than 1 year of age, and was associated with significantly poorer 1-year (50% vs. 85% no VT, P<0.01) and 5-year patient survival rates (50% vs. 83% no VT, P<0.01). One-year graft survival rates for FS grafts in recipients <12 months versus 12-23 months were 67% vs. 94% (P<0.01); the patient survival rate was also significantly lower in FS graft recipients <12 months (76% vs. 100%, P<0.05). Recipients <5 months of age had the worst survival rates: 1-year and 5-year patient survival rates were 65% and 46% for recipients 0-4 months (n=17) versus 82% and 82% for recipients 5-11 months (n=56), and 93% and 93% for recipients age 12-23 months (n=28; P<0.05). In summary, factors associated with reduced survival rates include recipient age <5 months, recipient age <12 months who received FS grafts, development of VT and donor weight <6 kg. There was a trend for UNOS status 1, fulminant hepatic failure, and presence of LPD to be associated with reduced survival rates.

  View details for PubMedID 9256181

• Use of an augmented urinary bladder can be catastrophic in renal transplantation XVI International Congress of the Transplantation-Society Alfrey, E. J., Conley, S. B., Tanney, D. C., Mak, R., Scandling, J. D., Dafoe, D. C., Hammer, G. B., Orlandi, P. D., Page, L., Salvatierra, O. ELSEVIER SCIENCE INC. 1997: 154–55

  View details for PubMedID 9122939

• Mechanical ventilation for pediatric patients INTERNATIONAL ANESTHESIOLOGY CLINICS Hammer, G. B., Frankel, L. R. 1997; 35 (1): 139-167

  View details for PubMedID 9113526

• Perioperative care of the neurosurgical pediatric patient INTERNATIONAL ANESTHESIOLOGY CLINICS Hammer, G. B., Krane, E. J. 1996; 34 (4): 55-71

  View details for PubMedID 8956064

• Continuous venovenous hemofiltration with dialysis in combination with total hepatectomy and portocaval shunting - Bridge to liver transplantation TRANSPLANTATION Hammer, G. B., So, S. K., ALUZRI, A., Conley, S. B., Concepcion, W., Cox, K. L., Berquist, W. E., Esquivel, C. O. 1996; 62 (1): 130-132

  Abstract

  Children who experience acute liver failure following liver transplantation will have multiple organ failure and a high rate of mortality unless emergency retransplantation can be performed. Transplant hepatectomy with portocaval shunting has been described as a bridge to transplantation in the most severe cases, as well as in patients with fulminant hepatic failure at high risk for mortality who have not undergone liver transplantation. Patients with multiple organ failure who have undergone hepatectomy require renal replacement therapy. Continuous hemofiltration may be used in patients with fulminant hepatic failure to facilitate fluid removal and circulatory and metabolic balance. We used continuous venovenous hemofiltration with dialysis following hepatectomy with portocaval shunting in a patient who remained anhepatic for 66 hr in order to achieve circulatory and metabolic homeostasis as well as stable neurologic function prior to successful retransplantation.

  View details for PubMedID 8693530

• Single-lung ventilation in pediatric patients ANESTHESIOLOGY Hammer, G. B., MANOS, S. J., Smith, B. M., Skarsgard, E. D., Brodsky, J. B. 1996; 84 (6): 1503-1506

  View details for PubMedID 8669693

• Ultra-high dose trimethaphan in an infant with severe hypertension JOURNAL OF TOXICOLOGY-CLINICAL TOXICOLOGY Hammer, G. B. 1996; 34 (2): 227-229

  Abstract

  Trimethaphan camsylate is a potent antihypertensive drug used to induce systemic arterial hypotension in patients undergoing major surgery and to treat severe systemic hypertension. The pharmacokinetics and pharmacodynamics of trimethaphan administered in the usual clinical dosages have been previously reported. The effects of trimethaphan when administered in very high doses of 500-1000 times the usual dose have not been reported.A case is presented of an infant with severe hypertension who inadvertently received such an overdose of trimethaphan.

  View details for PubMedID 8618259