- Critical Care Medicine
Clinical Assistant Professor, Emergency Medicine
Board Certification: Critical Care Medicine, American Board of Emergency Medicine (2015)
Fellowship:University of California - San Francisco (2014) CA
Board Certification: Emergency Medicine, American Board of Emergency Medicine (2013)
Residency:University of California - San Francisco (2012) CA
Medical Education:University of California - San Francisco (2008) CA
MS, University of California-Berkeley, School of Public Health, Health & Medical Sciences (2006)
Current Research and Scholarly Interests
Emergency critical care & resuscitation, ARDS, sepsis
Crystalloid Liberal or Vasopressors Early Resuscitation in Sepsis
Multicenter, prospective, phase 3 randomized non-blinded interventional trial of fluid treatment strategies in the first 24 hours for patients with sepsis-induced hypotension. The aim of the study is to determine the impact of a restrictive fluids strategy (vasopressors first followed by rescue fluids) as compared to a liberal fluid strategy (fluids first followed by rescue vasopressors) on 90-day in-hospital mortality in patients with sepsis-induced hypotension.
Vitamin C, Thiamine, and Steroids in Sepsis
The VItamin C, Thiamine And Steroids in Sepsis (VICTAS) Study is a double-blind, placebo-controlled, adaptive randomized clinical trial designed to investigate the efficacy of the combined use of vitamin C, thiamine and corticosteroids versus indistinguishable placebos for patients with sepsis. The objective of this study is to demonstrate the efficacy of combination therapy using vitamin C, thiamine and corticosteroids in reducing mortality and improving organ function in critically ill patients with sepsis.
Emergency Critical Care Intervention Study, Stanford University
We are studying the effects of ICU-trained RNs and MDs on outcomes for critically ill patients in the Emergency Department.
Stanford University Hospital
- Tsuyoshi Mitarai, Clinical Associate Professor, Emergency Medicine
- Jason Nesbitt, EMERGENCY SERVICES-SHC
- Michael Kohn, Clinical Professor, Emergency Medicine, Emergency Medicine
- Kian Niknam, Research Data Analyst I, Emergency Medicine, Emergency Medicine
- Christopher Cinkowski, EMERGENCY SERVICES-SHC
- Alfredo Urdaneta, Clinical Assistant Professor, Emergency Medicine
Graduate and Fellowship Programs
Critical Care Medicine (Fellowship Program)
Early High-Dose Vitamin D3 for Critically Ill, Vitamin D-Deficient Patients.
The New England journal of medicine
BACKGROUND: Vitamin D deficiency is a common, potentially reversible contributor to morbidity and mortality among critically ill patients. The potential benefits of vitamin D supplementation in acute critical illness require further study.METHODS: We conducted a randomized, double-blind, placebo-controlled, phase 3 trial of early vitamin D3 supplementation in critically ill, vitamin D-deficient patients who were at high risk for death. Randomization occurred within 12 hours after the decision to admit the patient to an intensive care unit. Eligible patients received a single enteral dose of 540,000 IU of vitamin D3 or matched placebo. The primary end point was 90-day all-cause, all-location mortality.RESULTS: A total of 1360 patients were found to be vitamin D-deficient during point-of-care screening and underwent randomization. Of these patients, 1078 had baseline vitamin D deficiency (25-hydroxyvitamin D level, <20 ng per milliliter [50 nmol per liter]) confirmed by subsequent testing and were included in the primary analysis population. The mean day 3 level of 25-hydroxyvitamin D was 46.9±23.2 ng per milliliter (117±58 nmol per liter) in the vitamin D group and 11.4±5.6 ng per milliliter (28±14 nmol per liter) in the placebo group (difference, 35.5 ng per milliliter; 95% confidence interval [CI], 31.5 to 39.6). The 90-day mortality was 23.5% in the vitamin D group (125 of 531 patients) and 20.6% in the placebo group (109 of 528 patients) (difference, 2.9 percentage points; 95% CI, -2.1 to 7.9; P=0.26). There were no clinically important differences between the groups with respect to secondary clinical, physiological, or safety end points. The severity of vitamin D deficiency at baseline did not affect the association between the treatment assignment and mortality.CONCLUSIONS: Early administration of high-dose enteral vitamin D3 did not provide an advantage over placebo with respect to 90-day mortality or other, nonfatal outcomes among critically ill, vitamin D-deficient patients. (Funded by the National Heart, Lung, and Blood Institute; VIOLET ClinicalTrials.gov number, NCT03096314.).
View details for DOI 10.1056/NEJMoa1911124
View details for PubMedID 31826336
End-of-Life Care, Palliative Care Consultation, and Palliative Care Referral in the Emergency Department: A Systematic Review.
Journal of pain and symptom management
CONTEXT: There is growing interest in providing palliative care (PC) in the emergency department (ED), but relatively little is known about the efficacy of ED-based PC interventions. A 2016 systematic review on this topic found no evidence that ED-based PC interventions affect patient outcomes or healthcare utilization, but new research has emerged since the publication of that review.OBJECTIVE: This systematic review provides a concise summary of current literature addressing the impact of ED-based PC interventions on patient- or family-reported outcomes, healthcare utilization, and survival.METHODS: We searched Pubmed, Embase, Web of Science, Scopus and CINAHL from inception until September 1, 2018 and reviewed references. Eligible articles evaluated the effects of PC interventions in the ED on patient- or family-reported outcomes, healthcare utilization, or survival.RESULTS: We screened 3091 abstracts and 98 full text articles with 13 articles selected for final inclusion. Two articles reported the results of a single RCT, while the remaining 11 studies were descriptive or quasi-experimental cohort studies. Over half of the included articles were published after the previous systematic review on this topic. Populations studied included older adults, patients with advanced malignancy, and ED patients screening positive for unmet palliative care needs. Most interventions involved referral to hospice or PC, or PC provided directly in the ED. Compared to usual care, ED-PC interventions improved quality of life, though this improvement was not observed when comparing ED-PC to inpatient-PC. ED-PC interventions expedited PC consultation; most studies reported a concomitant reduction in hospital length-of-stay and increase in hospice utilization, but some data were conflicting. Short-term mortality rates were high across all studies, but ED-PC interventions did not decrease survival time compared to usual care.CONCLUSION: Existing data support that PC in the ED is feasible, may improve quality of life, and does not appear to affect survival.
View details for DOI 10.1016/j.jpainsymman.2019.09.020
View details for PubMedID 31586580
Mechanical Ventilation in Hypoxemic Respiratory Failure.
Emergency medicine clinics of North America
2019; 37 (3): 431–44
Acute hypoxemic respiratory failure (AHRF) is a common challenge in emergency medicine. Patient outcomes depend on interventions performed during preintubation, intubation, and postintubation. The article presents recommendations for evidence-based practice to optimally manage patients with AHRF and the acute respiratory distress syndrome.
View details for DOI 10.1016/j.emc.2019.04.005
View details for PubMedID 31262413
- Treatment with allogeneic mesenchymal stromal cells for moderate to severe acute respiratory distress syndrome (START study): a randomised phase 2a safety trial LANCET RESPIRATORY MEDICINE 2019; 7 (2): 154–62
A Metagenomic Comparison of Tracheal Aspirate and Mini-Bronchial Alveolar Lavage for Assessment of Respiratory Microbiota.
American journal of physiology. Lung cellular and molecular physiology
Accurate and informative microbiologic testing is essential for guiding diagnosis and management of pneumonia in critically ill patients. Sampling of tracheal aspirate (TA) is less invasive compared to mini-bronchoalveolar lavage (mBAL) and is now recommended as a frontline diagnostic approach in mechanically ventilated patients, despite the historical belief that TA was suboptimal due to contamination from oral microbes. Advancements in metagenomic next generation sequencing (mNGS) now permit assessment of airway microbiota without a need for culture, and as such provide an opportunity to examine differences between mBAL and TA at a resolution previously unachievable. Here, we engaged shotgun mNGS to quantitatively assess the airway microbiome in matched mBAL and TA specimens from a prospective cohort of critically ill adults. We observed moderate differences betweensampletypes across all subjects, however we found significant compositional similarity in subjects with bacterial pneumonia, whose microbial communities were characterized by a dominant pathogen. In addition, we found that both mBAL and TA were similar in terms of microbialrelative abundance, abundance of oropharyngeal taxa, and microbial diversity. Our findings suggest that TA sampling provides a similar assessment of airway microbiota as more invasive testing by mBAL, and that this similarity is most significant in the setting of bacterial pneumonia.
View details for PubMedID 30652494
- Integrating host response and unbiased microbe detection for lower respiratory tract infection diagnosis in critically ill adults PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 2018; 115 (52): E12353–E12362
Critical Care Ultrasound: A Review for Practicing Nephrologists
ADVANCES IN CHRONIC KIDNEY DISEASE
2016; 23 (3): 141-145
The use of point-of-care ultrasound in the intensive care unit, both for diagnostic and procedural purposes, has rapidly proliferated, and evidence supporting its use is growing. Conceptually, critical care ultrasound (CCUS) should be considered an extension of the physical examination and should not be considered a replacement for formal echocardiography or radiology-performed ultrasound. Several CCUS applications are of particular relevance to nephrologists, including focused renal ultrasound in patients at high risk for urinary tract obstruction, real-time ultrasound guidance and verification during the placement of central venous catheters, and ultrasound-augmented assessment of shock and volume status. Each of these applications has the capacity to improve outcomes in patients with acute kidney injury. Although robust evidence regarding long-term outcomes is lacking, existing data demonstrate that CCUS has the potential to improve diagnostic accuracy, expedite appropriate management, and increase safety for critically ill patients across a spectrum of pathologies.
View details for DOI 10.1053/j.ackd.2016.01.015
View details for Web of Science ID 000375348600004
View details for PubMedID 27113689
Mesenchymal stem (stromal) cells for treatment of ARDS: a phase 1 clinical trial.
The Lancet. Respiratory medicine
2015; 3 (1): 24-32
No effective pharmacotherapy for acute respiratory distress syndrome (ARDS) exists, and mortality remains high. Preclinical studies support the efficacy of mesenchymal stem (stromal) cells (MSCs) in the treatment of lung injury. We aimed to test the safety of a single dose of allogeneic bone marrow-derived MSCs in patients with moderate-to-severe ARDS.The STem cells for ARDS Treatment (START) trial was a multicentre, open-label, dose-escalation, phase 1 clinical trial. Patients were enrolled in the intensive care units at University of California, San Francisco, CA, USA, Stanford University, Stanford, CA, USA, and Massachusetts General Hospital, Boston, MA, USA, between July 8, 2013, and Jan 13, 2014. Patients were included if they had moderate-to-severe ARDS as defined by the acute onset of the need for positive pressure ventilation by an endotracheal or tracheal tube, a PaO2:FiO2 less than 200 mm Hg with at least 8 cm H2O positive end-expiratory airway pressure (PEEP), and bilateral infiltrates consistent with pulmonary oedema on frontal chest radiograph. The first three patients were treated with low dose MSCs (1 million cells/kg predicted bodyweight [PBW]), the next three patients received intermediate dose MSCs (5 million cells/kg PBW), and the final three patients received high dose MSCs (10 million cells/kg PBW). Primary outcomes included the incidence of prespecified infusion-associated events and serious adverse events. The trial is registered with ClinicalTrials.gov, number NCT01775774.No prespecified infusion-associated events or treatment-related adverse events were reported in any of the nine patients. Serious adverse events were subsequently noted in three patients during the weeks after the infusion: one patient died on study day 9, one patient died on study day 31, and one patient was discovered to have multiple embolic infarcts of the spleen, kidneys, and brain that were age-indeterminate, but thought to have occurred before the MSC infusion based on MRI results. None of these severe adverse events were thought to be MSC-related.A single intravenous infusion of allogeneic, bone marrow-derived human MSCs was well tolerated in nine patients with moderate to severe ARDS. Based on this phase 1 experience, we have proceeded to phase 2 testing of MSCs for moderate to severe ARDS with a primary focus on safety and secondary outcomes including respiratory, systemic, and biological endpoints.The National Heart, Lung, and Blood Institute.
View details for DOI 10.1016/S2213-2600(14)70291-7
View details for PubMedID 25529339
Biomarkers in acute respiratory distress syndrome: from pathobiology to improving patient care
EXPERT REVIEW OF RESPIRATORY MEDICINE
2014; 8 (5): 573-586
Acute respiratory distress syndrome (ARDS) is a clinical syndrome characterized by alveolar flooding with protein-rich pulmonary edema fluid. Despite an improved understanding of ARDS pathogenesis, our ability to predict the development of ARDS and risk-stratify patients with the disease remains limited. Biomarkers may help identify patients at highest risk of developing ARDS, assess response to therapy, predict outcome, and optimize enrollment in clinical trials. This review begins with a general description of biomarker use in clinical medicine. We then review evidence that supports the value of various ARDS biomarkers organized by the cellular injury processes central to ARDS development: endothelial injury, epithelial injury, disordered inflammation and coagulation, fibrosis, and apoptosis. Finally, we summarize the growing contributions of genomic and proteomic research and suggest ways in which the field may evolve in the coming years.
View details for DOI 10.1586/17476348.2014.924073
View details for Web of Science ID 000342062700007
View details for PubMedID 24875533
Human mesenchymal stem cells reduce the severity of acute lung injury in a sheep model of bacterial pneumonia
2014; 69 (9): 819-825
Human bone marrow-derived mesenchymal stem (stromal) cells (hMSCs) improve survival in mouse models of acute respiratory distress syndrome (ARDS) and reduce pulmonary oedema in a perfused human lung preparation injured with Escherichia coli bacteria. We hypothesised that clinical grade hMSCs would reduce the severity of acute lung injury (ALI) and would be safe in a sheep model of ARDS.Adult sheep (30-40 kg) were surgically prepared. After 5 days of recovery, ALI was induced with cotton smoke insufflation, followed by instillation of live Pseudomonas aeruginosa (2.5×10(11) CFU) into both lungs under isoflurane anaesthesia. Following the injury, sheep were ventilated, resuscitated with lactated Ringer's solution and studied for 24 h. The sheep were randomly allocated to receive one of the following treatments intravenously over 1 h in one of the following groups: (1) control, PlasmaLyte A, n=8; (2) lower dose hMSCs, 5×10(6) hMSCs/kg, n=7; and (3) higher-dose hMSCs, 10×10(6) hMSCs/kg, n=4.By 24 h, the PaO2/FiO2 ratio was significantly improved in both hMSC treatment groups compared with the control group (control group: PaO2/FiO2 of 97±15 mm Hg; lower dose: 288±55 mm Hg (p=0.003); higher dose: 327±2 mm Hg (p=0.003)). The median lung water content was lower in the higher-dose hMSC-treated group compared with the control group (higher dose: 5.0 g wet/g dry [IQR 4.9-5.8] vs control: 6.7 g wet/g dry [IQR 6.4-7.5] (p=0.01)). The hMSCs had no adverse effects.Human MSCs were well tolerated and improved oxygenation and decreased pulmonary oedema in a sheep model of severe ARDS.NCT01775774 for Phase 1. NCT02097641 for Phase 2.
View details for DOI 10.1136/thoraxjnl-2013-204980
View details for Web of Science ID 000340239900009
View details for PubMedID 24891325
View details for PubMedCentralID PMC4284068
- Design and implementation of the START (STem cells for ARDS Treatment) trial, a phase 1/2 trial of human mesenchymal stem/stromal cells for the treatment of moderate-severe acute respiratory distress syndrome ANNALS OF INTENSIVE CARE 2014; 4
OBLIQUE-AXIS VS. SHORT-AXIS VIEW IN ULTRASOUND-GUIDED CENTRAL VENOUS CATHETERIZATION
JOURNAL OF EMERGENCY MEDICINE
2014; 47 (1): 45-50
Ultrasound (US) guidance during central venous catheterization (CVC) reduces complications and improves success rates compared to landmark-guided techniques. A novel "oblique view" (US transducer held at approximately 45° with respect to the target vessel) has been suggested to be superior to the standard short-axis approach usually used during US-guided CVC.The purpose of this study was to compare the rates of posterior vessel wall puncture (PVWP) between the short-axis and oblique-axis approaches to US-guided CVC.This was a prospective observational trial of emergency medicine residents and attending physicians, using gelatin models to simulate short-axis and oblique-axis US-guided CVC. Participants were blinded to the primary outcome of PVWP. Data collected included year in training/practice, number of central lines placed, time to successful "flash," and self-reported confidence of needle tip position using a Likert scale. After CVC simulation, models were deconstructed and inspected for PVWP.The rate of PVWP was 14.7% using short axis vs. 2.9% using oblique axis, resulting in a difference of 11.8% (95% confidence interval [CI] -4.7-28.3%, p = 0.10) and an odds ratio of 0.2 (95% CI 0.004-1.79). This difference was not statistically significant (p = 0.10). Mean time to flash was 11.9 s using short axis, and 15.4 s using oblique axis (p = 0.14). Confidence in needle tip location was 3.63 using short axis, and 4.58 using oblique axis (p < 0.001).We found decreased PVWP using the oblique axis approach, though the difference was not statistically significant, and participants felt more confident in their needle tip location using the oblique axis view. Further research into the potential benefits of the oblique axis approach is warranted.
View details for DOI 10.1016/j.jemermed.2013.11.080
View details for Web of Science ID 000338476500017
View details for PubMedID 24685453
Impaired Visual Fixation at the Age of 2 Years in Children Born Before the Twenty-Eighth Week of Gestation. Antecedents and Correlates in the Multi Center ELGAN Study
2014; 51 (1): 36-42
Very little is known about the prevalence, antecedents, and correlates of impaired visual fixation in former very preterm newborns.In the multicenter ELGAN study sample of 1057 infants born before the twenty-eighth week of gestation who had a developmental assessment at 2 years corrected age, we identified 73 who were unable to follow an object across the midline. We compared them to the 984 infants who could follow an object across the midline.In this sample of very preterm newborns, those who had impaired visual fixation were much more likely than those without impaired visual fixation to have been born after the shortest of gestations (odds ratio, 3.2; 99% confidence interval, 1.4-7.5) and exposed to maternal aspirin (odds ratio, 5.2; 99% confidence interval, 2.2-12). They were also more likely than their peers to have had prethreshold retinopathy of prematurity (odds ratio, 4.1; 99% confidence interval, 1.8-9.0). At age 2 years, the children with impaired fixation were more likely than others to be unable to walk (even with assistance) (odds ratio, 7.5; 99% confidence interval, 2.2-26) and have a Mental Development Index more than three standard deviations below the mean of a normative sample (odds ratio, 3.6; 99% confidence interval, 1.4-8.2).Risk factors for brain and retinal damages, such as very low gestational age, appear to be risk factors for impaired visual fixation. This inference is further supported by the co-occurrence at age 2 years of impaired visual fixation, inability to walk, and a very low Mental Development Index.
View details for DOI 10.1016/j.pediatrneurol.2014.03.007
View details for Web of Science ID 000338174800008
View details for PubMedID 24938138
View details for PubMedCentralID PMC4062923
Design and implementation of the START (STem cells for ARDS Treatment) trial, a phase 1/2 trial of human mesenchymal stem/stromal cells for the treatment of moderate-severe acute respiratory distress syndrome.
Annals of intensive care
2014; 4: 22-?
Despite advances in supportive care, moderate-severe acute respiratory distress syndrome (ARDS) is associated with high mortality rates, and novel therapies to treat this condition are needed. Compelling pre-clinical data from mouse, rat, sheep and ex vivo perfused human lung models support the use of human mesenchymal stem (stromal) cells (MSCs) as a novel intravenous therapy for the early treatment of ARDS.This article describes the study design and challenges encountered during the implementation and phase 1 component of the START (STem cells for ARDS Treatment) trial, a phase 1/2 trial of bone marrow-derived human MSCs for moderate-severe ARDS. A trial enrolling 69 subjects is planned (9 subjects in phase 1, 60 subjects in phase 2 treated with MSCs or placebo in a 2:1 ratio).This report describes study design features that are unique to a phase 1 trial in critically ill subjects and the specific challenges of implementation of a cell-based therapy trial in the ICU.Experience gained during the design and implementation of the START study will be useful to investigators planning future phase 1 clinical trials based in the ICU, as well as trials of cell-based therapy for other acute illnesses.NCT01775774 and NCT02097641.
View details for DOI 10.1186/s13613-014-0022-z
View details for PubMedID 25593740
Evolving practices in critical care and their influence on acute kidney injury
CURRENT OPINION IN CRITICAL CARE
2013; 19 (6): 523-530
This review highlights the principal advances in critical care over the past year, and discusses the impact of these advances on the diagnosis and management of acute kidney injury (AKI).Recent literature has focused on assessment of volume status and fluid management, particularly in the setting of respiratory and cardiac failure. Other critical care topics are reviewed using a system-based approach.The incidence of AKI appears to be increasing, and despite advances in the provision of critical care and renal replacement therapies, there has been little improvement in its associated morbidity and mortality. Nonetheless, recent advances in critical care will impact the diagnosis and management of AKI, as well as shape the future research agenda. Continued work in the fields of critical care and nephrology will undoubtedly be centered on improved biomarkers for the detection of AKI, specific therapies to mitigate or reverse AKI, and techniques to prevent the development of AKI in the critically ill population.
View details for DOI 10.1097/MCC.0000000000000040
View details for Web of Science ID 000330358100001
View details for PubMedID 24240818
- Cardiac tamponade. The western journal of emergency medicine 2013; 14 (2): 152-?