Omar Lateef

Efficacy and safety of dopamine versus norepinephrine in the management of septic shock.

The optimum septic shock vasopressor support strategy is currently debated. This study was performed to evaluate the efficacy and safety of norepinephrine (NE) and dopamine (DA) as the initial vasopressor in septic shock patients who were managed with a specific treatment protocol. A prospective, randomized, open-label, clinical trial was used in a medical intensive care unit comparing DA with NE as the initial vasopressor in fluid-resuscitated 252 adult patients with septic shock. If the maximum dose of the initial vasopressor was unable to maintain the hemodynamic goal, then fixed-dose vasopressin was added to each regimen. If additional vasopressor support was needed to achieve the hemodynamic goal, then phenylephrine was added. The primary efficacy end point was all-cause 28-day mortality. Secondary end points included organ dysfunction, hospital and intensive care unit length of stay, and safety (primarily occurrence of arrhythmias). The 28-day mortality rate was 50% (67/134) with DA as the initial vasopressor compared with 43% (51/118) for NE treatment (P = 0.282). There was a significantly greater incidence of sinus tachycardia with DA (24.6%; 33/134) than NE (5.9%; 7/118) and arrhythmias noted with DA treatment (19.4%; 26/134) compared with NE treatment (3.4%; 4/118; P < 0.0001), respectively. Logistic regression analysis identified Acute Physiologic and Chronic Health Evaluation II score (P < 0.0001) and arrhythmia (P < 0.015) as significant predictors of outcome. In this protocol-directed vasopressor support strategy for septic shock, DA and NE were equally effective as initial agents as judged by 28-day mortality rates. However, there were significantly more cardiac arrhythmias with DA treatment. Patients receiving DA should be monitored for the development of cardiac arrhythmias (NCT00604019).

Methotrexate pulmonary toxicity

Methotrexate is a commonly prescribed antineoplastic and immune modulating compound that has gained wide acceptance in the management of rheumatoid arthritis, psoriasis, sarcoidosis and a number of neoplastic disorders. Although generally considered safe and easy to use, methotrexate has been associated with a number of adverse reactions. Pulmonary toxicity has been well-described and may take a variety of forms. Pulmonary infiltrates are the most commonly encountered form of methotrexate pulmonary toxicity and these infiltrates resemble hypersensitivity lung disease. This discussion focuses primarily on low-dose methotrexate pulmonary toxicity and will discuss the diagnosis using clinical, pulmonary function, radiographical and pathological manifestations. Suggestions for clinical monitoring to detect adverse effects are given. In addition, management of pulmonary toxicity through discontinuation of the methotrexate, support and possibly the administration of corticosteroids is discussed.

Reducing Use of Indwelling Urinary Catheters and Associated Urinary Tract Infections

BACKGROUND Use of indwelling urinary catheters can lead to complications, most commonly catheter-associated urinary tract infections. Duration of catheterization is the major risk factor. These infections can result in sepsis, prolonged hospitalization, additional hospital costs, and mortality. OBJECTIVES To implement and evaluate the efficacy of an intervention to reduce catheter-associated urinary tract infections in a medical intensive care unit by decreasing use of urinary catheters. METHODS Indications for continuing urinary catheterization with indwelling devices were developed by unit clinicians. For a 6-month intervention period, patients in a medical intensive care unit who had indwelling urinary catheters were evaluated daily by using criteria for appropriate catheter continuance. Recommendations were made to discontinue indwelling urinary catheters in patients who did not meet the criteria. Days of use of a urinary catheter and rates of catheter-associated urinary tract infections during the intervention were compared with those of the preceding 11 months. RESULTS During the study period, 337 patients had a total of 1432 days of urinary catheterization. With use of guidelines, duration of use was significantly reduced to a mean of 238.6 d/mo from the previous rate of 311.7 d/mo. The number of catheter-associated urinary tract infections per 1000 days of use was a mean of 4.7/mo before the intervention and zero during the 6-month intervention period. CONCLUSIONS Implementation of an intervention to judge appropriateness of indwelling urinary catheters may result in significant reductions in duration of catheterization and occurrences of catheter-associated urinary tract infections.

Intensive Nutrition in Acute Lung Injury A Clinical Trial (INTACT)

BACKGROUND Despite extensive use of enteral (EN) and parenteral nutrition (PN) in intensive care unit (ICU) populations for 4 decades, evidence to support their efficacy is extremely limited. METHODS A prospective randomized trial was conducted evaluate the impact on outcomes of intensive medical nutrition therapy (IMNT; provision of >75% of estimated energy and protein needs per day via EN and adequate oral diet) from diagnosis of acute lung injury (ALI) to hospital discharge compared with standard nutrition support care (SNSC; standard EN and ad lib feeding). The primary outcome was infections; secondary outcomes included number of days on mechanical ventilation, in the ICU, and in the hospital and mortality. RESULTS Overall, 78 patients (40 IMNT and 38 SNSC) were recruited. No significant differences between groups for age, body mass index, disease severity, white blood cell count, glucose, C-reactive protein, energy or protein needs occurred. The IMNT group received significantly higher percentage of estimated energy (84.7% vs 55.4%, P < .0001) and protein needs (76.1 vs 54.4%, P < .0001) per day compared with SNSC. No differences occurred in length of mechanical ventilation, hospital or ICU stay, or infections. The trial was stopped early because of significantly greater hospital mortality in IMNT vs SNSC (40% vs 16%, P = .02). Cox proportional hazards models indicated the hazard of death in the IMNT group was 5.67 times higher (P = .001) than in the SNSC group. CONCLUSIONS Provision of IMNT from ALI diagnosis to hospital discharge increases mortality.

Impact of the Implementation of a Sepsis Protocol for the Management of Fluid-Refractory Septic Shock: A Single-Center, Before-and-After Study

BACKGROUND Evidence-based guidelines have been published for the acute management of severe sepsis and septic shock. Key goals of institution-driven protocols include timely fluid resuscitation and antibiotic selection, as well as source control. OBJECTIVE This study assessed the impact of a sepsis protocol on the timeliness of antibiotic administration, the adequacy of fluid resuscitation, and 28-day mortality in patients with fluid-refractory septic shock. METHODS This was a single-center, before-and-after study (18 months before July 2007 and 18 months after) with prospective data collection evaluating the outcomes of a sepsis protocol in adult patients with fluid-refractory septic shock. All patients received a fluid challenge and antibiotics; those who did not were excluded from this analysis. Preprotocol findings led to the development of the sepsis protocol, which emphasized fluid resuscitation, timely administration of antibiotic therapy, and collection of specimens for culture at the onset of septic shock. In the pre- and postprotocol phases of the study, data were collected prospectively and analyzed for demographic characteristics; Acute Physiology and Chronic Health Evaluation (APACHE) II score; appropriateness of fluid resuscitation; antibiotic use; number of vasopressor, ventilator, and intensive care unit (ICU) days; and 28-day mortality. Outcomes were measured prospectively at any time during the patients hospital admission. The primary end points were the time to administration of antimicrobial therapy and the appropriateness of fluid resuscitation before and after implementation of the sepsis protocol. RESULTS A total of 118 patients were included in the analysis: 64 and 54 in the pre- and postprotocol groups, respectively. Patients in the preprotocol group were primarily women (53% [34/64]) and had a mean (SD) age of 61 (15.5) years and a mean APACHE II score of 28 (6.0). Patients in the postprotocol group were primarily men (54% [29/54]) and had a mean age of 52 (18.0) years and a mean APACHE II score of 27 (6.4). Implementation of the sepsis protocol resulted in a greater percentage of patients receiving timely antibiotic therapy (ie, within 4.5 hours of refractory shock; 85% [46/54] vs 56% [36/64]; P = 0.001) and adequate fluid resuscitation (72% [39/54] vs 31% [20/64]; P < 0.001) compared with the preprotocol group. Post hoc analysis found significant decreases in the number of vasopressor days (mean [SD], 3.8 [2.7] to 1.4 [1.5]; P < 0.001), ventilator days (9.1 [12.2] to 2.7 [4.0]; P < 0.001), and ICU days (12.3 [12.6] to 4.9 [3.9]; P < 0.001) in the postprotocol group. In-hospital mortality was not significantly different between the groups (survival 46% [28/61] before vs 54% [33/61] after the protocol). Multivariate analysis for predictors of in-hospital mortality identified an interval between shock and empiric antibiotic administration of >4.5 hours (odds ratio [OR] = 5.54; 95% CI, 1.91-16.07; P < 0.002), vasopressor duration in days (OR = 1.27; 95% CI, 1.01-1.59; P = 0.037), APACHE II score (OR = 1.14; 95% CI, 1.05-1.24; P = 0.003), and type of infection (community vs nosocomial, OR = 0.18; 95% CI, 0.05-0.61; P = 0.006) as significant predictors. The 28-day mortality decreased from 61% (39/64) to 33% (18/54) after implementation of the protocol (P = 0.004). CONCLUSION Implementation of a sepsis protocol emphasizing early administration of antibiotic therapy and adequate fluid resuscitation was associated with improved clinical outcomes and lower 28-day mortality in patients with fluid-refractory septic shock at this institution.

Assessing the influence of registered dietitian order-writing privileges on parenteral nutrition use.

Previous studies have examined the influence of a nutrition support team on parenteral nutrition (PN) use; however, the influence of registered dietitian (RD) order-writing privileges on appropriate PN use has yet to be reported. A retrospective cohort was conducted at a single tertiary care urban academic medical center to compare adult PN use before RD order-writing privileges (January 1, 2003 to December 31, 2004, pre-privileges) to after RD order-writing privileges (January 1, 2006 to December 31, 2007, post-privileges). RD order-writing privileges were obtained June 2005; PN patients during the washout period (January 1, 2005 to December 31, 2005) were not included. Descriptive statistics were conducted (N=1,965 patients). Although total hospital admissions increased from the pre-privileges to post-privileges periods (P<0.0001), overall PN use decreased from 1,080 patients during the pre-privileges period to 885 patients during the post-privileges period (P<0.0001). Inappropriate PN use decreased from 482 (45%) to 240 (27%) patients (P<0.0001) during the pre- and post-privileges periods, respectively. Among inappropriate PN use, there was a decrease in PN administration for patients with poor oral intake (130 to 41 patients), pancreatitis (78 to 26 patients), intractable nausea and vomiting (68 to 23 patients), and mucositis (56 to 18 patients; all Ps<0.0003), reflecting a 20% cost savings for PN. No significant differences were found in hospital length of stay, admissions to intensive care units, or other infectious complications between the two periods. RDs with order-writing privileges can decrease inappropriate PN use and costs in a hospital setting. Future studies should continue to highlight the influence of RDs in these advanced practice roles, as well as other members of the nutrition support team, especially with regard to nutrition support delivery and patient outcomes.

Role of timing and dose of energy received in patients with acute lung injury on mortality in the Intensive Nutrition in Acute Lung Injury Trial (INTACT): A post hoc analysis

BACKGROUND Our trial INTACT (Intensive Nutrition in Acute Lung Injury Trial) was designed to compare the impact of feeding from acute lung injury (ALI) diagnosis to hospital discharge, an interval that, to our knowledge, has not yet been explored. It was stopped early because participants who were randomly assigned to energy intakes at nationally recommended amounts via intensive medical nutrition therapy experienced significantly higher mortality hazards than did those assigned to standard nutrition support care that provided energy at 55% of recommended concentrations. OBJECTIVE We assessed the influence of dose and timing of feeding on hospital mortality. DESIGN Participants (n = 78) were dichotomized as died or discharged alive. Associations between the energy and protein received overall, early (days 1-7), and late (days ≥8) and the hazards of hospital mortality were evaluated between groups with multivariable analysis methods. RESULTS Higher overall energy intake predicted significantly higher mortality (OR: 1.14, 95% CI: 1.02, 1.27). Among participants enrolled for ≥8 d (n = 66), higher early energy intake significantly increased the HR for mortality (HR: 1.17, 95% CI: 1.07, 1.28), whereas higher late energy intake was significantly protective (HR: 0.91, 95% CI: 0.83, 1.0). Results were similar for early but not late protein (grams per kilogram) exposure (early-exposure HR: 8.9, 95% CI: 2.3, 34.3; late-exposure HR: 0.15, 95% CI: 0.02, 1.1). Threshold analyses indicated early mean intakes ≥18 kcal/kg significantly increased subsequent mortality. CONCLUSIONS Providing kilocalories per kilogram or grams of protein per kilogram early post-ALI diagnosis at recommended levels was associated with significantly higher hazards for mortality, whereas higher late energy intakes reduced mortality hazards. This time-varying effect violated the Cox proportionality assumption, indicating that feeding trials in similar populations should extend beyond 7 d and use time-varying statistical methods. Future trials are required for corroboration. INTACT was registered at clinicaltrials.gov as NCT01921101.

Attitudes Toward and Experiences in End-of-life Care Education in the Intensive Care Unit A Survey of Resident Physicians

Introduction: Resident physicians provide the most physician care to intensive care unit (ICU) patients. The body of literature about residents’ palliative and end-of-life care (PC/EOLC) experiences in the ICU is limited. To our knowledge, this is the first study to assess resident physicians in multiple specialties regarding PC/EOLC in the ICU. Methods: A Web-based survey was developed and administered to all resident physicians in a single academic institution who had completed at least 1 dedicated ICU rotation. Results: Residents reported moderate comfort in dealing with end-of-life (EOL) issues and felt somewhat prepared to care for critically ill patients at the EOL. Feedback should be provided to residents regarding their PC/EOLC skills, and education should be tailored to residents rotating in the ICU.

A Novel Expression of Exercise Induced Pulmonary Hypertension in Human Immunodeficiency Virus Patients: A Pilot Study

Background: Patients with the human immunodeficiency virus (HIV) are at risk for multiple pulmonary complications including pulmonary hypertension. Exercise induced pulmonary hypertension (EIPH) has been previously described in patients with scleroderma, sickle cell disease and chronic obstructive pulmonary disease, yet has not been associated with the HIV population. Methods: A prospective case-control study design was implemented. Four HIV patients with unexplained dyspnea and four healthy controls underwent symptom-limited stationary bicycle exercise. Transthoracic Doppler Echocardiography was used to measure tricuspid regurgitation velocity which was used to calculate the right ventricular to right atrial pressure (RV-RA) gradient at rest and at peak exercise using the simplified Bernoulli’s equation. Change in RV-RA gradient between rest and peak exercise was calculated and considered to represent change in pulmonary arterial systolic pressure. Results: The mean age was 41.25 years (±8.7) for patients and 33.5 years (±6.0) for controls. The mean CD4 count of patients was 191.5 cells/μL (±136.2). Patients had a significantly higher increase in RV-RA gradient as compared to controls (180.2% vs. 27.5%, p = 0.03). Discussion: This pilot study suggests that it is feasible to use recumbent bicycle and transthoracic Doppler echocardiography for the evaluation of EIPH among HIV patients with dyspnea of unknown etiology. The study is too small to draw any broad conclusion. Further evaluation of this concept with a larger study is warranted.

Early Exposure to Recommended Calorie Delivery in the Intensive Care Unit Is Associated With Increased Mortality in Patients With Acute Respiratory Distress Syndrome

BACKGROUND The Intensive Nutrition in Acute Lung Injury: Clinical Trial (INTACT), designed to evaluate outcomes of calorie delivery from acute respiratory distress syndrome (ARDS) diagnosis through hospital discharge, was stopped due to higher mortality in the intervention group. Post hoc analysis found timing and dose of calorie delivery influenced mortality. The objective of this retrospective cohort study was to determine if early vs late calorie exposure changed the hazard of death among a larger sample of patients with ARDS. METHODS Adult patients who met the eligibility criteria for INTACT but did not participate were included. Daily calorie delivery was collected from the date INTACT eligibility was determined to extubation or death. Cox proportional hazards regression was used to model the relationship between hazard of hospital death with average calorie exposure received over increasing study days and after day 7. RESULTS A total of 298 patients were included; overall mortality was 33%. Among patients who remained intubated at 1 week (n = 202), higher kcal/kg received from intensive care unit (ICU) days 1-6 increased hazards of subsequent death on days 7+ (hazard ratio [HR], 1.04; 95% confidence interval [CI], 1.01-1.06); kcal/kg received after ICU day 7 decreased the hazards of death on day 7+ (HR, 0.53; 95% CI, 0.33-0.84). CONCLUSIONS Higher calorie exposure between ICU days 1 and 7 was associated with higher subsequent hazard of mortality, and provision of high-calorie exposure after day 8 decreased the hazards of death.