Eliotte L. Hirshberg

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.

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.

Diastolic dysfunction and mortality in early severe sepsis and septic shock: a prospective, observational echocardiography study

BackgroundPatients with severe sepsis or septic shock often exhibit significant cardiovascular dysfunction. We sought to determine whether severity of diastolic dysfunction assessed by transthoracic echocardiography (TTE) predicts 28-day mortality.MethodsIn this prospective, observational study conducted in two intensive care units at a tertiary care hospital, 78 patients (age 53.2 ± 17.1 years; 51% females; mean APACHE II score 23.3 ± 7.4) with severe sepsis or septic shock underwent TTE within 6 h of ICU admission, after 18 to 32 h, and after resolution of shock. Left ventricular (LV) diastolic dysfunction was defined according to modified American Society of Echocardiography 2009 guidelines using E, A, and e’ velocities; E/A and E/e’; and E deceleration time. Systolic dysfunction was defined as an ejection fraction < 45%.ResultsTwenty-seven patients (36.5%) had diastolic dysfunction on initial echocardiogram, while 47 patients (61.8%) had diastolic dysfunction on at least one echocardiogram. Total mortality was 16.5%. The highest mortality (37.5%) was observed among patients with grade I diastolic dysfunction, an effect that persisted after controlling for age and APACHE II score. At time of initial TTE, central venous pressure (CVP) (11+/- 5 mmHg) did not differ among grades I-III, although patients with grade I received less intravenous fluid.ConclusionsLV diastolic dysfunction is common in septic patients. Grade I diastolic dysfunction, but not grades II and III, was associated with increased mortality. This finding may reflect inadequate fluid resuscitation in early sepsis despite an elevated CVP, suggesting a possible role for TTE in sepsis resuscitation.

Tight glycemic control in critically Ill children

Background In multicenter studies, tight glycemic control targeting a normal blood glucose level has not been shown to improve outcomes in critically ill adults or children after cardiac surgery. Studies involving critically ill children who have not undergone cardiac surgery are lacking. Methods In a 35‐center trial, we randomly assigned critically ill children with confirmed hyperglycemia (excluding patients who had undergone cardiac surgery) to one of two ranges of glycemic control: 80 to 110 mg per deciliter (4.4 to 6.1 mmol per liter; lower‐target group) or 150 to 180 mg per deciliter (8.3 to 10.0 mmol per liter; higher‐target group). Clinicians were guided by continuous glucose monitoring and explicit methods for insulin adjustment. The primary outcome was the number of intensive care unit (ICU)–free days to day 28. Results The trial was stopped early, on the recommendation of the data and safety monitoring board, owing to a low likelihood of benefit and evidence of the possibility of harm. Of 713 patients, 360 were randomly assigned to the lower‐target group and 353 to the higher‐target group. In the intention‐to‐treat analysis, the median number of ICU‐free days did not differ significantly between the lower‐target group and the higher‐target group (19.4 days [interquartile range {IQR}, 0 to 24.2] and 19.4 days [IQR, 6.7 to 23.9], respectively; P=0.58). In per‐protocol analyses, the median time‐weighted average glucose level was significantly lower in the lower‐target group (109 mg per deciliter [IQR, 102 to 118]; 6.1 mmol per liter [IQR, 5.7 to 6.6]) than in the higher‐target group (123 mg per deciliter [IQR, 108 to 142]; 6.8 mmol per liter [IQR, 6.0 to 7.9]; P<0.001). Patients in the lower‐target group also had higher rates of health care–associated infections than those in the higher‐target group (12 of 349 patients [3.4%] vs. 4 of 349 [1.1%], P=0.04), as well as higher rates of severe hypoglycemia, defined as a blood glucose level below 40 mg per deciliter (2.2 mmol per liter) (18 patients [5.2%] vs. 7 [2.0%], P=0.03). No significant differences were observed in mortality, severity of organ dysfunction, or the number of ventilator‐free days. Conclusions Critically ill children with hyperglycemia did not benefit from tight glycemic control targeted to a blood glucose level of 80 to 110 mg per deciliter, as compared with a level of 150 to 180 mg per deciliter. (Funded by the National Heart, Lung, and Blood Institute and others; HALF‐PINT ClinicalTrials.gov number, NCT01565941.)

Moderate Glucose Control Is Associated With Increased Mortality Compared With Tight Glucose Control in Critically Ill Patients Without Diabetes

BACKGROUND Optimal glucose management in the ICU remains unclear. In 2009, many clinicians at Intermountain Healthcare selected a moderate glucose control (90-140 mg/dL) instead of tight glucose control (80-110 mg/dL). We hypothesized that moderate glucose control would affect patients with and without preexisting diabetes differently. METHODS We performed a retrospective cohort analysis of all patients treated with eProtocol-insulin from November 2006 to March 2011, stratifying for diabetes. We performed multivariate logistic regression for 30-day mortality with covariates of age, modified APACHE (Acute Physiology and Chronic Health Evaluation) II score, Charlson Comorbidity score, and target glucose. RESULTS We studied 3,529 patients in 12 different ICUs in eight different hospitals. Patients with diabetes had higher mean glucose (132 mg/dL vs 124 mg/dL) and greater glycemic variability (SD = 41 mg/dL vs 29 mg/dL) than did patients without diabetes (P < .01 for both comparisons). Tight glucose control was associated with increased frequency of moderate and severe hypoglycemia (30.3% and 3.6%) compared with moderate glucose control (14.3% and 2.0%, P < .01 for both). Multivariate analysis demonstrated that the moderate glucose target was independently associated with increased risk of mortality in patients without diabetes (OR, 1.36; 95% CI, 1.01-1.84; P = .05) but decreased risk of mortality in patients with diabetes (OR, 0.65; 95% CI, 0.45-0.93; P = .01). CONCLUSIONS Moderate glucose control (90-140 mg/dL) may confer greater mortality in critically ill patients without diabetes compared with tight glucose control (80-110 mg/dL). A single glucose target does not appear optimal for all critically ill patients. These data have important implications for the design of future interventional trials as well as for the glycemic management of critically ill patients.

Right and Left Heart Failure in Severe H1N1 Influenza A Infection

Influenza infection can affect cardiac function. The recent pandemic of H1N1 influenza A provided an opportunity to study echocardiographic findings in critically ill infected patients. We hypothesised that critically ill patients with H1N1 infection would have a higher incidence of right and left heart failure than is seen in unselected populations of patients with septic shock and/or acute respiratory distress syndrome (ARDS). We retrospectively studied all patients admitted to four intensive care units at three hospitals in Salt Lake County, UT, USA, with laboratory-confirmed H1N1 infection in whom a clinical echocardiogram was available. 23 out of 48 patients had qualifying echocardiograms. Right ventricular (RV) dilatation (50–80%) and at least moderate systolic impairment (23%) were common, higher than the range described in general populations with ARDS. Left ventricular systolic dysfunction was present in 17% of patients. No single echocardiographic parameter was associated with 28-day mortality or ventilator-free days to 28 days. Critically ill patients with H1N1 infection frequently exhibit right heart dilatation and failure. RV basal dilatation was extremely common. These patients have less left heart failure than expected on the basis of prior descriptions of influenza myopericarditis or of general populations of septic patients.

Clinical equipoise regarding glycemic control: a survey of pediatric intensivist perceptions.

Objectives: To assess the willingness of pediatric intensivists to conduct a pediatric trial of blood glucose control, and to determine if self-reported practices were influenced by adult-specific data over the past 4 yrs. This was a follow-up to our previous 2005 survey. Design: Electronic survey comprising a 30-item questionnaire. Setting: North American PICUs that were members of, or connected to, the Pediatric Acute Lung Injury and Sepsis Network (n = 96 targeted institutions). Participants: North American pediatric intensivists (n = 209). Interventions: None. Methods: We conducted a survey of North American PICUs using a Web-based questionnaire. Invitations were sent to 96 institutions in 37 states/provinces. Results: Response rate was 68% (141/209). The median definitions of hyperglycemia (150 mg/dL) and hypoglycemia (⩽60 mg/dL) were similar to our 2005 survey results. Self-reported practice patterns remain variable. Although 75% of clinician respondents denied a change in clinical practice based on the published literature, the preferred blood glucose target range increased from 80–110 mg/dL in 2005 to 90–140 mg/dL in 2009. Intensivists who preferred a blood glucose target of 80–110 mg/dL decreased from 43% to 6% (p < 0.001). Many respondents (45%) indicated that the acceptable severe hypoglycemia rate (% patients) for a protocol was ⩽2.5%. The majority (93%) indicated they would be willing to enroll patients in a pediatric trial of blood glucose control. Conclusions: Pediatric intensivists report that they control blood glucose with insulin in critically ill children and do not necessarily adopt adult-specific data or a single uniform blood glucose target. The published evidence does not adequately address PICU clinicians concerns. Unanswered questions and persistent variation in practice suggest a need for a multicenter clinical trial of blood glucose control in critically ill children.

The evolution of eProtocols that enable reproducible clinical research and care methods

Unnecessary variation in clinical care and clinical research reduces our ability to determine what healthcare interventions are effective. Reducing this unnecessary variation could lead to further healthcare quality improvement and more effective clinical research. We have developed and used electronic decision support tools (eProtocols) to reduce unnecessary variation. Our eProtocols have progressed from a locally developed mainframe computer application in one clinical site (LDS Hospital) to web-based applications available in multiple languages and used internationally. We use eProtocol-insulin as an example to illustrate this evolution. We initially developed eProtocol-insulin as a local quality improvement effort to manage stress hyperglycemia in the adult intensive care unit (ICU). We extended eProtocol-insulin use to translate our quality improvement results into usual clinical care at Intermountain Healthcare ICUs. We exported eProtocol-insulin to support research in other US and international institutions, and extended our work to the pediatric ICU. We iteratively refined eProtocol-insulin throughout these transitions, and incorporated new knowledge about managing stress hyperglycemia in the ICU. Based on our experience in the development and clinical use of eProtocols, we outline remaining challenges to eProtocol development, widespread distribution and use, and suggest a process for eProtocol development. Technical and regulatory issues, as well as standardization of protocol development, validation and maintenance, need to be addressed. Resolution of these issues should facilitate general use of eProtocols to improve patient care.

Hyperglycemia: an independent risk factor for poor outcome in children with traumatic brain injury*.

Objective: We sought 1) to describe the severity and duration of hyperglycemia among surviving and dying children after traumatic brain injury; 2) to evaluate whether persistent severe hyperglycemia (averaged blood glucose > 200 mg/dL [11 mmol/L] during the first 12 hr after injury) is independently associated with poor Glasgow Outcome Score; and 3) to evaluate different definitions and the prevalence of poor Glasgow Outcome Score to better understand measurement and potential hyperglycemia treatment evaluation. Design: Retrospective cohort. Setting: Level I American College of Surgery verified pediatric trauma center. Patients: Children admitted to intensive care with moderate-to-severe traumatic brain injury. Interventions: None. Measurements and Main Results: Time course for glucose changes was compared by survival and blood glucose groups. Twelve-hour averaged patient blood glucoses were categorized as persistent: severe hyperglycemia (> 200 mg/dL [11 mmol/L]), moderate hyperglycemia (161–200 mg/dL [9–11 mmol/L]), mild hyperglycemia (110–160 mg/dL [6–9 mmol/L]), normal glycemia (80–109 mg/dL [4–6 mmol/L]), or hypoglycemia (< 80 mg/dL [< 4 mmol/L]). Among 271 children, less than 1% had hypoglycemia and were excluded from further analysis. Seven percent had normal, 49% had mild, 24% had moderate, and 20% had severe blood glucose elevation. Among dying children (n = 44, 16%), the mean blood glucose at 20–24 hours after injury was significantly greater compared with survivors (150 vs 113 mg/dL [8 vs 6 mmol/L]) but by 29–32 hours, no longer significantly differed (112 vs 102 mg/dL [6 mmol/L]). Sixty-eight percent of children with severe blood glucose elevation had a poor outcome, whereas good outcomes at discharge occurred in 87% with mild or moderate blood glucose elevation. Severe blood glucose elevation was associated with a 3.5-fold increased adjusted odds ratio of poor outcome (95% CI, 1.2–10.3) compared with mild blood glucose elevation adjusted for injury severity and cardiorespiratory instability. Conclusions: Duration of severe blood glucose elevation (blood glucose > 200 mg/dL [11 mmol/L]) was brief but remained independently associated with poor outcome.