Colin K. Grissom

Wilderness medical society consensus guidelines for the prevention and treatment of acute altitude illness

To provide guidance to clinicians about best practices, the Wilderness Medical Society (WMS) convened an expert panel to develop evidence-based guidelines for the prevention and treatment of acute mountain sickness (AMS), high altitude cerebral edema (HACE), and high altitude pulmonary edema (HAPE). These guidelines present the main prophylactic and therapeutic modalities for each disorder and provide recommendations for their roles in disease management. Recommendations are graded based on the quality of supporting evidence and balance between the benefits and risks/burdens according to criteria put forth by the American College of Chest Physicians. The guidelines also provide suggested approaches to the prevention and management of each disorder that incorporate these recommendations.

Acetazolamide in the Treatment of Acute Mountain Sickness: Clinical Efficacy and Effect on Gas Exchange

OBJECTIVE To determine the efficacy of acetazolamide in the treatment of patients with acute mountain sickness and the effect of the drug on pulmonary gas exchange in acute mountain sickness. DESIGN A randomized, double-blind, placebo-controlled trial. SETTING The Denali Medical Research Project high-altitude research station (4200 m) on Mt. McKinley, Alaska. PARTICIPANTS Twelve climbers attempting an ascent of Mt. McKinley (summit, 6150 m) who presented to the medical research station with acute mountain sickness. INTERVENTION Climbers were randomly assigned to receive acetazolamide, 250 mg orally, or placebo at 0 (baseline) and 8 hours after inclusion in the study. MAIN OUTCOME MEASURES An assessment of acute mountain sickness using a symptom score and pulmonary gas exchange measurements was done at baseline and at 24 hours. MAIN RESULTS After 24 hours, five of six climbers treated with acetazolamide were healthy, whereas all climbers who received placebo still had acute mountain sickness (P = 0.015). Arterial blood gas specimens were obtained from three of the six acetazolamide recipients and all of the placebo recipients. The alveolar to arterial oxygen pressure difference (PAO2-PaO2 difference) decreased slightly over 24 hours in the acetazolamide group (-0.8 +/- 1.2 mm Hg) but increased in the placebo group (+3.3 +/- 2.3 mm Hg) (P = 0.024). Acetazolamide improved PaO2 over 24 hours (+2.9 +/- 0.8 mm Hg) when compared with placebo (-1.3 +/- 2.8 mm Hg) (P = 0.045). CONCLUSION In established cases of acute mountain sickness, treatment with acetazolamide relieves symptoms, improves arterial oxygenation, and prevents further impairment of pulmonary gas exchange.

Clinical Findings and Demographic Factors Associated With ICU Admission in Utah Due to Novel 2009 Influenza A(H1N1) Infection

BACKGROUND Novel 2009 influenza A(H1N1) infection has significantly affected ICUs. We sought to characterize our regions clinical findings and demographic associations with ICU admission due to novel A(H1N1). METHODS We conducted an observational study from May 19, 2009, to June 30, 2009, of descriptive clinical course, inpatient mortality, financial data, and demographic characteristics of an ICU cohort. A case-control study was used to compare the ICU cohort to Salt Lake County residents. RESULTS The ICU cohort of 47 influenza patients had a median age of 34 years, Acute Physiology and Chronic Health Evaluation II score of 21, and BMI of 35 kg/m2. Mortality was 17% (8/47). All eight deaths occurred among the 64% of patients (n = 30) with ARDS, 26 (87%) of whom also developed multiorgan failure. Compared with the Salt Lake County population, patients with novel A(H1N1) were more likely to be obese (22% vs 74%; P < .001), medically uninsured (14% vs 45%; P < .001), and Hispanic (13% vs 23%; P < .01) or Pacific Islander (1% vs 26%; P < .001). Observed ICU admissions were 15-fold greater than expected for those with BMI > or = 40 kg/m2 (standardized morbidity ratio 15.8, 95% CI, 8.3-23.4) and 1.5-fold greater than expected among those with BMI of 30 to 39 kg/m(2) for age-adjusted and sex-adjusted rates for Salt Lake County. CONCLUSIONS Severe ARDS with multiorgan dysfunction in the absence of bacterial infection was a common clinical presentation. In this cohort, young nonwhites without medical insurance were disproportionately likely to require ICU care. Obese patients were particularly susceptible to critical illness due to novel A(H1N1) infection.

A replicable method for blood glucose control in critically Ill patients.

Context:To ensure interpretability and replicability of clinical experiments, methods must be adequately explicit and should elicit the same decision from different clinicians who comply with the study protocol. Objective:The objective of this study was to determine whether clinician compliance with protocol recommendations exceeds 90%. Design:We developed an adequately explicit computerized protocol (eProtocol-insulin) for managing critically ill adult patient blood glucose. We monitored clinician compliance with eProtocol-insulin recommendations in four intensive care units in four hospitals and compared blood glucose distributions with those of a simple clinical guideline at one hospital and a paper-based protocol at another. All protocols and the guideline used intravenous insulin and 80 to 110 mg/dL (4.4–6.1 mmol/L) blood glucose targets. Setting:The setting for this study was four academic hospital intensive care units. Patients:This study included critically ill adults requiring intravenous insulin. Intervention:Intervention used in this study was a bedside computerized protocol for managing blood glucose. Main Outcome Measure:The main outcome measure was clinician compliance with eProtocol-insulin recommendations. Results:The number of patients was 31 to 458 and the number of blood glucose measurements was 2,226 to 19,925 among the four intensive care units. Clinician compliance with eProtocol-insulin recommendations was 91% to 98%. Blood glucose distributions were similar in the four hospitals (generalized linear model p = .18). Compared with the simple guideline, eProtocol-insulin glucose measurements within target increased from 21% to 39%, and mean blood glucose decreased from 142 to 115 mg/dL (generalized linear model p < .001). Compared with the paper-based protocol, eProtocol-insulin glucose measurements within target increased from 28% to 42%, and mean blood glucose decreased from 134 to 116 mg/dL (generalized linear model p = .001). Conclusions:The 91% to 98% clinician compliance indicates eProtocol-insulin is an exportable instrument that can establish a replicable experimental method for clinical trials of blood glucose management in critically ill adults. Control of blood glucose was better with eProtocol-insulin than with a simple clinical guideline or a paper-based protocol.

Wilderness Medical Society Practice Guidelines for the Prevention and Treatment of Acute Altitude Illness: 2014 Update

To provide guidance to clinicians about best practices, the Wilderness Medical Society convened an expert panel to develop evidence-based guidelines for prevention and treatment of acute mountain sickness, high altitude cerebral edema, and high altitude pulmonary edema. These guidelines present the main prophylactic and therapeutic modalities for each disorder and provide recommendations about their role in disease management. Recommendations are graded based on the quality of supporting evidence and balance between the benefits and risks/burdens according to criteria put forth by the American College of Chest Physicians. The guidelines also provide suggested approaches to prevention and management of each disorder that incorporate these recommendations. This is an updated version of the original WMS Consensus Guidelines for the Prevention and Treatment of Acute Altitude Illness published in Wilderness & Environmental Medicine 2010;21(2):146-155.

The septic milieu triggers expression of spliced tissue factor mRNA in human platelets

Summary.  Background: Activated platelets have previously‐unrecognized mechanisms of post‐transcriptional gene expression that may influence hemostasis and inflammation. A novel pathway involves splicing of pre‐mRNAs in resting platelets to mature, translatable mRNAs in response to cellular activation. Objectives: We asked if bacterial products and host agonists present in the septic milieu induce tissue factor pre‐mRNA splicing in platelets from healthy subjects. In parallel, we asked if spliced tissue factor (TF) mRNA is present in platelets from septic patients in a proof‐of‐principle analysis. Patients/methods: TF pre‐mRNA and mRNA expression patterns were characterized in platelets from septic patients and in platelets isolated from healthy subjects activated with bacteria, toxins and inflammatory agonists. Procoagulant activity was also measured. Results and conclusions: Live bacteria, staphylococcal α‐toxin and lipopolysaccharide (LPS) induced TF pre‐mRNA splicing in platelets isolated from healthy subjects. Toxin‐stimulated platelets accelerated plasma clotting, a response that was blocked by a previously‐characterized splicing inhibitor and by an anti‐tissue factor antibody. Platelets from septic patients expressed spliced TF mRNA, whereas it was absent from unselected and age‐matched control subjects. Tissue factor‐dependent procoagulant activity was elevated in platelets from a subset of septic patients. Thus, bacterial and host factors induce splicing of TF pre‐mRNA, expression of TF mRNA and tissue factor‐dependent clotting activity in human platelets. TF mRNA is present in platelets from some septic patients, indicating that it may be a marker of altered platelet phenotype and function in sepsis and that splicing pathways are induced in this syndrome.

Update on High-Altitude Pulmonary Edema: Pathogenesis, Prevention, and Treatment

Abstract High-altitude pulmonary edema (HAPE) is a life-threatening noncardiogenic form of pulmonary edema (PE) that afflicts susceptible persons after rapid ascent to high altitude above 2500 m. Its pathogenesis is related to increased sympathetic tone, exaggerated hypoxic pulmonary vasoconstriction, uneven hypoxic pulmonary vasoconstriction with overperfusion of some regions of the pulmonary vascular bed, increased pulmonary capillary pressure, stress failure of pulmonary capillaries, and alveolar fluid leak across capillary endothelium resulting in interstitial and alveolar edema. Prevention of HAPE is most effectively achieved by gradual ascent with time for acclimatization, although recent small studies have highlighted a number of pharmacologic options. Inhaled salmeterol prevents HAPE presumably by increasing alveolar fluid clearance, the phosphodiesterase-5 inhibitor tadalafil works by acting as a pulmonary vasodilator, and dexamethasone seems to prevent HAPE by stabilizing the capillary endothelium, along with other potential effects. These investigations have yet to be validated in widespread clinical practice. Nifedipine, which prevents HAPE via its effects as a pulmonary vasodilator, has a longer history of clinical use. The most effective and reliable treatment of established HAPE is immediate descent and/or adequate flow supplemental oxygen to maintain arterial saturation above 90%, accompanied by rest from strenuous physical activity. Use of a portable hyperbaric chamber is an effective temporizing measure, and nifedipine may be used for treatment of HAPE, although only as an adjunct to descent and/or supplemental oxygen if these methods of treatment are not immediately available to a person with HAPE.

Wilderness Medical Society Practice Guidelines for the Prevention and Treatment of Frostbite

The Wilderness Medical Society convened an expert panel to develop a set of evidence-based guidelines for the prevention and treatment of frostbite. We present a review of pertinent pathophysiology. We then discuss primary and secondary prevention measures and therapeutic management. Recommendations are made regarding each treatment and its role in management. These recommendations are graded based on the quality of supporting evidence and balance between the benefits and risks/burdens for each modality according to methodology stipulated by the American College of Chest Physicians.

Applying dynamic parameters to predict hemodynamic response to volume expansion in spontaneously breathing patients with septic shock.

ABSTRACT Volume expansion is a mainstay of therapy in septic shock, although its effect is difficult to predict using conventional measurements. Dynamic parameters, which vary with respiratory changes, appear to predict hemodynamic response to fluid challenge in mechanically ventilated, paralyzed patients. Whether they predict response in patients who are free from mechanical ventilation is unknown. We hypothesized that dynamic parameters would be predictive in patients not receiving mechanical ventilation. This is a prospective, observational, pilot study. Patients with early septic shock and who were not receiving mechanical ventilation received 10-mL/kg volume expansion (VE) at their treating physician’s discretion after initial resuscitation in the emergency department. We used transthoracic echocardiography to measure vena cava collapsibility index and aortic velocity variation before VE. We used a pulse contour analysis device to measure stroke volume variation (SVV). Cardiac index was measured immediately before and after VE using transthoracic echocardiography. Hemodynamic response was defined as an increase in cardiac index 15% or greater. Fourteen patients received VE, five of whom demonstrated a hemodynamic response. Vena cava collapsibility index and SVV were predictive (area under the curve = 0.83, 0.92, respectively). Optimal thresholds were calculated: vena cava collapsibility index, 15% or greater (positive predictive value, 62%; negative predictive value, 100%; P = 0.03); SVV, 17% or greater (positive predictive value 100%, negative predictive value 82%, P = 0.03). Aortic velocity variation was not predictive. Vena cava collapsibility index and SVV predict hemodynamic response to fluid challenge patients with septic shock who are not mechanically ventilated. Optimal thresholds differ from those described in mechanically ventilated patients.

Survival After Shock Requiring High-Dose Vasopressor Therapy

BACKGROUND Some patients with hypotensive shock do not respond to usual doses of vasopressor therapy. Very little is known about outcomes after high-dose vasopressor therapy (HDV). We sought to characterize survival among patients with shock requiring HDV. We also evaluated the possible utility of stress-dose corticosteroid therapy in these patients. METHODS We conducted a retrospective study of patients with shock requiring HDV in the ICUs of five hospitals from 2005 through 2010. We defined HDV as receipt at any point of ≥ 1 μg/kg/min of norepinephrine equivalent (calculated by summing norepinephrine-equivalent infusion rates of all vasopressors). We report survival 90 days after hospital admission. We evaluated receipt of stress-dose corticosteroids, cause of shock, receipt of CPR, and withdrawal or withholding of life support therapy. RESULTS We identified 443 patients meeting inclusion criteria. Seventy-six (17%) survived. Survival was similar (20%) among the 241 patients with septic shock. Among the 367 nonsurvivors, 254 (69%) experienced withholding/withdrawal of care, and 115 (31%) underwent CPR. Stress-dose corticosteroid therapy was associated with increased survival (P = .01). CONCLUSIONS One in six patients with shock survived to 90 days after HDV. The majority of nonsurvivors died after withdrawal or withholding of life support therapy. A minority of patients underwent CPR. Additionally, stress-dose corticosteroid therapy appears reasonable in patients with shock requiring HDV.