Stanley A. Nasraway

Clinical practice guidelines for the sustained use of sedatives and analgesics in the critically ill adult

Judith Jacobi, PharmD, FCCM, BCPS; Gilles L. Fraser, PharmD, FCCM; Douglas B. Coursin, MD; Richard R. Riker, MD; Dorrie Fontaine, RN, DNSc, FAAN; Eric T. Wittbrodt, PharmD; Donald B. Chalfin, MD, MS, FCCM; Michael F. Masica, MD, MPH; H. Scott Bjerke, MD; William M. Coplin, MD; David W. Crippen, MD, FCCM; Barry D. Fuchs, MD; Ruth M. Kelleher, RN; Paul E. Marik, MDBCh, FCCM; Stanley A. Nasraway, Jr, MD, FCCM; Michael J. Murray, MD, PhD, FCCM; William T. Peruzzi, MD, FCCM; Philip D. Lumb, MB, BS, FCCM. Developed through the Task Force of the American College of Critical Care Medicine (ACCM) of the Society of Critical Care Medicine (SCCM), in collaboration with the American Society of Health-System Pharmacists (ASHP), and in alliance with the American College of Chest Physicians; and approved by the Board of Regents of ACCM and the Council of SCCM and the ASHP Board of Directors

Double-blind randomised controlled trial of monoclonal antibody to human tumour necrosis factor in treatment of septic shock

Summary Background Despite the availability of potent antibiotics and intensive care, mortality rates from septic shock are 40–70%. We assessed the safety and efficacy of murine monoclonal antibody to human tumour necrosis factor α (TNF α MAb) in the treatment of septic shock. Methods In a randomised, multicentre, double-blind, placebo-controlled clinical trial in 105 hospitals in the USA and Canada, we randomly assigned 1879 patients a single infusion of 7·5 mg/kg TNFα MAb (n=949) or placebo (0·25% human serum albumin n=930). Our main outcome measurement was the rate of all-cause mortality at 28 days. Findings 382 (40·3%) of 948 patients who received TNFα MAb and 398 (42·8%) of 930 who received placebo had died at 28 days (95% CI −0·02 to 0·07, p=0·27). We found no association between therapy with TNFα MAb and increased rapidity in reversal of initial shock or prevention of subsequent shock. Similarly, baseline plasma interleukin-6 concentrations of more than 1000 pg/mL or detectable circulating TNF concentrations were not associated with improvement in survival after TNFα MAb therapy. Coagulopathy but not other organ or system failures, was significantly decreased in the TNFα MAb group compared with placebo (day 7, p Interpretation We did not find an improvement in survival after septic shock with TNFα MAb. Therapy not solely dependent on TNFα blockade may be required to improve survival.

Clinical practice guidelines for sustained neuromuscular blockade in the adult critically ill patient

Objective:To update the 2002 version of “Clinical practice guidelines for sustained neuromuscular blockade in the adult critically ill patient.” Design:A Task Force comprising 17 members of the Society of Critical Medicine with particular expertise in the use of neuromuscular-blocking agents; a Grading of Recommendations Assessment, Development, and Evaluation expert; and a medical writer met via teleconference and three face-to-face meetings and communicated via e-mail to examine the evidence and develop these practice guidelines. Annually, all members completed conflict of interest statements; no conflicts were identified. This activity was funded by the Society for Critical Care Medicine, and no industry support was provided. Methods:Using the Grading of Recommendations Assessment, Development, and Evaluation system, the Grading of Recommendations Assessment, Development, and Evaluation expert on the Task Force created profiles for the evidence related to six of the 21 questions and assigned quality-of-evidence scores to these and the additional 15 questions for which insufficient evidence was available to create a profile. Task Force members reviewed this material and all available evidence and provided recommendations, suggestions, or good practice statements for these 21 questions. Results:The Task Force developed a single strong recommendation: we recommend scheduled eye care that includes lubricating drops or gel and eyelid closure for patients receiving continuous infusions of neuromuscular-blocking agents. The Task Force developed 10 weak recommendations. 1) We suggest that a neuromuscular-blocking agent be administered by continuous intravenous infusion early in the course of acute respiratory distress syndrome for patients with a PaO2/FIO2 less than 150. 2) We suggest against the routine administration of an neuromuscular-blocking agents to mechanically ventilated patients with status asthmaticus. 3) We suggest a trial of a neuromuscular-blocking agents in life-threatening situations associated with profound hypoxemia, respiratory acidosis, or hemodynamic compromise. 4) We suggest that neuromuscular-blocking agents may be used to manage overt shivering in therapeutic hypothermia. 5) We suggest that peripheral nerve stimulation with train-of-four monitoring may be a useful tool for monitoring the depth of neuromuscular blockade but only if it is incorporated into a more inclusive assessment of the patient that includes clinical assessment. 6) We suggest against the use of peripheral nerve stimulation with train of four alone for monitoring the depth of neuromuscular blockade in patients receiving continuous infusion of neuromuscular-blocking agents. 7) We suggest that patients receiving a continuous infusion of neuromuscular-blocking agent receive a structured physiotherapy regimen. 8) We suggest that clinicians target a blood glucose level of less than 180 mg/dL in patients receiving neuromuscular-blocking agents. 9) We suggest that clinicians not use actual body weight and instead use a consistent weight (ideal body weight or adjusted body weight) when calculating neuromuscular-blocking agents doses for obese patients. 10) We suggest that neuromuscular-blocking agents be discontinued at the end of life or when life support is withdrawn. In situations in which evidence was lacking or insufficient and the study results were equivocal or optimal clinical practice varies, the Task Force made no recommendations for nine of the topics. 1) We make no recommendation as to whether neuromuscular blockade is beneficial or harmful when used in patients with acute brain injury and raised intracranial pressure. 2) We make no recommendation on the routine use of neuromuscular-blocking agents for patients undergoing therapeutic hypothermia following cardiac arrest. 3) We make no recommendation on the use of peripheral nerve stimulation to monitor degree of block in patients undergoing therapeutic hypothermia. 4) We make no recommendation on the use of neuromuscular blockade to improve the accuracy of intravascular-volume assessment in mechanically ventilated patients. 5) We make no recommendation concerning the use of electroencephalogram-derived parameters as a measure of sedation during continuous administration of neuromuscular-blocking agents. 6) We make no recommendation regarding nutritional requirements specific to patients receiving infusions of neuromuscular-blocking agents. 7) We make no recommendation concerning the use of one measure of consistent weight over another when calculating neuromuscular-blocking agent doses in obese patients. 8) We make no recommendation on the use of neuromuscular-blocking agents in pregnant patients. 9) We make no recommendation on which muscle group should be monitored in patients with myasthenia gravis receiving neuromuscular-blocking agents. Finally, in situations in which evidence was lacking or insufficient but expert consensus was unanimous, the Task Force developed six good practice statements. 1) If peripheral nerve stimulation is used, optimal clinical practice suggests that it should be done in conjunction with assessment of other clinical findings (e.g., triggering of the ventilator and degree of shivering) to assess the degree of neuromuscular blockade in patients undergoing therapeutic hypothermia. 2) Optimal clinical practice suggests that a protocol should include guidance on neuromuscular-blocking agent administration in patients undergoing therapeutic hypothermia. 3) Optimal clinical practice suggests that analgesic and sedative drugs should be used prior to and during neuromuscular blockade, with the goal of achieving deep sedation. 4) Optimal clinical practice suggests that clinicians at the bedside implement measure to attenuate the risk of unintended extubation in patients receiving neuromuscular-blocking agents. 5) Optimal clinical practice suggests that a reduced dose of an neuromuscular-blocking agent be used for patients with myasthenia gravis and that the dose should be based on peripheral nerve stimulation with train-of-four monitoring. 6) Optimal clinical practice suggests that neuromuscular-blocking agents be discontinued prior to the clinical determination of brain death.

Guidelines for the use of an insulin infusion for the management of hyperglycemia in critically ill patients.

Objective:To evaluate the literature and identify important aspects of insulin therapy that facilitate safe and effective infusion therapy for a defined glycemic end point. Methods:Where available, the literature was evaluated using Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) methodology to assess the impact of insulin infusions on outcome for general intensive care unit patients and those in specific subsets of neurologic injury, traumatic injury, and cardiovascular surgery. Elements that contribute to safe and effective insulin infusion therapy were determined through literature review and expert opinion. The majority of the literature supporting the use of insulin infusion therapy for critically ill patients lacks adequate strength to support more than weak recommendations, termed suggestions, such that the difference between desirable and undesirable effect of a given intervention is not always clear. Recommendations:The article is focused on a suggested glycemic control end point such that a blood glucose ≥150 mg/dL triggers interventions to maintain blood glucose below that level and absolutely <180 mg/dL. There is a slight reduction in mortality with this treatment end point for general intensive care unit patients and reductions in morbidity for perioperative patients, postoperative cardiac surgery patients, post-traumatic injury patients, and neurologic injury patients. We suggest that the insulin regimen and monitoring system be designed to avoid and detect hypoglycemia (blood glucose ⩽70 mg/dL) and to minimize glycemic variability.Important processes of care for insulin therapy include use of a reliable insulin infusion protocol, frequent blood glucose monitoring, and avoidance of finger-stick glucose testing through the use of arterial or venous glucose samples. The essential components of an insulin infusion system include use of a validated insulin titration program, availability of appropriate staffing resources, accurate monitoring technology, and standardized approaches to infusion preparation, provision of consistent carbohydrate calories and nutritional support, and dextrose replacement for hypoglycemia prevention and treatment. Quality improvement of glycemic management programs should include analysis of hypoglycemia rates, run charts of glucose values <150 and 180 mg/dL. The literature is inadequate to support recommendations regarding glycemic control in pediatric patients. Conclusions:While the benefits of tight glycemic control have not been definitive, there are patients who will receive insulin infusion therapy, and the suggestions in this article provide the structure for safe and effective use of this therapy.

Prior Environmental Contamination Increases the Risk of Acquisition of Vancomycin-Resistant Enterococci

BACKGROUND Patients colonized with vancomycin-resistant enterococci (VRE) frequently contaminate their environment, but the environmental role of VRE transmission remains controversial. METHODS During a 14-month study in 2 intensive care units, weekly environmental and twice-weekly patient surveillance cultures were obtained. VRE acquisition was defined as a positive culture result >48 h after admission. To determine risk factors for VRE acquisition, Cox proportional hazards models using time-dependent covariates for colonization pressure and antibiotic exposure were examined. RESULTS Of 1330 intensive care unit admissions, 638 patients were at risk for acquisition, and 50 patients (8%) acquired VRE. Factors associated with VRE acquisition included average colonization pressure (hazard ratio [HR], 1.4 per 10% increase; 95% confidence interval [CI], 1.2-1.8), mean number of antibiotics (HR, 1.7 per additional antibiotic; 95% CI, 1.2-2.5), leukemia (HR, 3.1; 95% CI, 1.2-7.8), a VRE-colonized prior room occupant (HR, 3.1; 95% CI, 1.6-5.8), any VRE-colonized room occupants within the previous 2 weeks (HR, 2.5; 95% CI, 1.3-4.8), and previous positive room culture results (HR, 3.4; 95% CI, 1.2-9.6). In separate multivariable analyses, a VRE-colonized prior room occupant (HR, 3.8; 95% CI, 2.0-7.4), any VRE-colonized room occupants within the previous 2 weeks (HR, 2.7; 95% CI, 1.4-5.3), and previous positive room culture results (HR, 4.4; 95% CI, 1.5-12.8) remained independent predictors of VRE acquisition, adjusted for colonization pressure and antibiotic exposure. CONCLUSIONS We found that prior room contamination, whether measured via environmental cultures or prior room occupancy by VRE-colonized patients, was highly predictive of VRE acquisition. Increased attention to environmental disinfection is warranted.

How reliable is the Bispectral Index in critically ill patients? A prospective, comparative, single-blinded observer study.

Objective To establish a correlation between a reliable subjective measure, the Sedation-Agitation Scale (SAS), and an objective tool, the Bispectral Index (BIS), for monitoring critically ill patients with a decreased level of consciousness. Design Prospective, comparative, single-blinded observer study. Setting Surgical and medical intensive care units of the Tufts-New England Medical Center, a 349-bed tertiary care, academic medical center. Patients A convenience sample of 20 adult, critically ill patients with a decreased level of consciousness. The data from one patient were excluded because the patient did not meet inclusion criteria. Measurements and Main Results Patients were prospectively evaluated by a blinded observer using the SAS to subjectively determine their level of consciousness. Sedation levels varied from unarousable (SAS score of 1), to very sedated (SAS score of 2), to mildly sedated (SAS score of 3). Simultaneously, the patients were continuously monitored for 4–6 hrs with the BIS device. There was wide variability in BIS scores for any given level of consciousness as compared with the SAS. Unarousable patients had BIS scores ranging from 23 to 97, with a median score of 50 and an interquartile range of 24. Very sedated patients had BIS scores ranging from 35 to 98, with a median score of 68 and an interquartile range of 36. Mildly sedated patients had BIS scores ranging from 67 to 91, with a median score of 76 and an interquartile range of 8. Overall, there was a less than satisfactory correlation between BIS values and SAS scores (r = .36, p < .001). However, the correlation improved with subgroup analysis when BIS values associated with excessive muscle movement were excluded (r = .50, p < .001). Conclusions The correlation between SAS and BIS scores was suboptimal and inconsistent in a heterogeneous group of critically ill patients. The generation of BIS hardware and software, studied herein, is neither reliable nor valid for routinely monitoring the level of consciousness in the critically ill patient. Excessive muscle movement by the patient is an important and spurious influence on BIS values and seriously undermines BIS reliability.

Morbid obesity is an independent determinant of death among surgical critically ill patients.

Objective:To determine whether extreme obesity (morbid obesity; body mass index ≥40 kg/m2) is an independent risk factor for death among critically ill patients; this objective is most salient in the subset of patients who sustain a prolonged intensive care unit stay during which the burdens of care imposed by obesity and its consequences would become most apparent. Design:Cohort analysis of data from the Project Impact database used to catalog admissions and outcomes to a surgical intensive care unit, with predetermined end point analyses of outcomes. Setting:Surgical intensive care unit serving Tufts-New England Medical Center, a tertiary care and university medical center in Boston. Patients:All critically ill surgical patients admitted to the Tufts-New England Medical Center surgical intensive care unit from January 1998 to March 2001. Interventions:Intensive care unit and hospital mortality and lengths of stay were compared with body mass index subclassified into five groups: underweight, normal weight, overweight, obese, and extremely obese. Data were examined for all admissions during the study period and for a predetermined subgroup with a prolonged intensive care unit stay (≥4 days). Measurements and Main Results:The prevalence of obesity in the surgical intensive care unit was 26.7%; extreme obesity was observed in 6.8%. In the full cohort of patients (n = 1373), median length of stay was short (2 days) and there were no differences in mortality in patients among any of the body mass index classes. In the subgroup of prolonged stay patients (n = 406), intensive care unit and hospital mortality rates were significantly increased in extremely obese patients compared with all other patients (intensive care unit, 33.3% vs. 12.3%, p = .009; hospital, 33.3% vs. 16%, p = .045). Multivariate analysis showed that extreme obesity was an independent predictor of death in surgical critically ill patients with prolonged intensive care unit stay after controlling for age, gender, and severity of illness. The odds of death increased 7.4 times in patients with morbid obesity. Conclusions:Morbid obesity (body mass index ≥40 kg/m2) is an independent risk factor for death in surgical patients with catastrophic illness requiring prolonged intensive care. The prevalence of obesity is growing, both in the intensive care unit and in the general population. The increased risk of complications and death in this population mandates that we adapt customized processes of care to specifically address this unique and very challenging subset of patients.

Diabetic status and the relation of the three domains of glycemic control to mortality in critically ill patients: an international multicenter cohort study.

IntroductionHyperglycemia, hypoglycemia, and increased glycemic variability have each beenindependently associated with increased risk of mortality in critically illpatients. The role of diabetic status on modulating the relation of these threedomains of glycemic control with mortality remains uncertain. The purpose of thisinvestigation was to determine how diabetic status affects the relation ofhyperglycemia, hypoglycemia, and increased glycemic variability with the risk ofmortality in critically ill patients.MethodsThis is a retrospective analysis of prospectively collected data involving 44,964patients admitted to 23 intensive care units (ICUs) from nine countries, betweenFebruary 2001 and May 2012. We analyzed mean blood glucose concentration (BG),coefficient of variation (CV), and minimal BG and created multivariable models toanalyze their independent association with mortality. Patients were stratifiedaccording to the diagnosis of diabetes.ResultsAmong patients without diabetes, mean BG bands between 80 and 140 mg/dl wereindependently associated with decreased risk of mortality, and mean BG bands> 140 mg/dl, with increased risk of mortality. Among patients withdiabetes, mean BG from 80 to 110 mg/dl was associated with increased risk ofmortality and mean BG from 110 to 180 mg/dl with decreased risk of mortality. Aneffect of center was noted on the relation between mean BG and mortality.Hypoglycemia, defined as minimum BG <70 mg/dl, was independently associatedwith increased risk of mortality among patients with and without diabetes andincreased glycemic variability, defined as CV > 20%, was independentlyassociated with increased risk of mortality only among patients without diabetes.Derangements of more than one domain of glycemic control had a cumulativeassociation with mortality, especially for patients without diabetes.ConclusionsAlthough hyperglycemia, hypoglycemia, and increased glycemic variability is eachindependently associated with mortality in critically ill patients, diabeticstatus modulates these relations in clinically important ways. Our findingssuggest that patients with diabetes may benefit from higher glucose target rangesthan will those without diabetes. Additionally, hypoglycemia is independentlyassociated with increased risk of mortality regardless of the patients diabeticstatus, and increased glycemic variability is independently associated withincreased risk of mortality among patients without diabetes.See related commentary by Krinsley,http://ccforum.com/content/17/2/131See related commentary by Finfer and Billot,http://ccforum.com/content/17/2/134

Guidelines on admission and discharge for adult intermediate care units

OBJECTIVE To present guidelines for writing admission and discharge policies for adult intermediate care units. DATA SOURCES Opinion of practitioners with experience and expertise in managing critical and intermediate care units. DATA SYNTHESIS Consensus was reached regarding the characteristics of patients best suited for management in an intermediate care unit, as supported by a literature review. CONCLUSION Criteria were developed that define patients who are optimal candidates for management in an intermediate care unit.

Conduction Disturbances Associated with Administration of Butyrophenone Antipsychotics in the Critically Ill: A Review of the Literature

Droperidol and haloperidol have demonstrated efficacy and safety in the treatment of acute delirium in critically ill patients. We conducted MEDLINE and manual searches of literature published from 1966–1996 to identify articles describing conduction disturbances associated with the drugs. The objectives were to describe the proposed mechanisms of acquired long QTc interval syndrome and torsades de pointes, and to recommend how critically ill patients receiving these agents should be monitored. We found 11 published reports of conduction disturbances associated with intravenous administration of droperidol or haloperidol. The majority of cases occurred in critically ill patients prescribed more than 50 mg/24 hours of either agent. Of the 18 patients described, 13 (72%) had a history of cardiovascular disease. Based on the small number of available case reports, it seems reasonable to suggest that the incidence of adverse cardiovascular effects due to droperidol and haloperidol is small. The mechanism of butyrophenone‐induced QTc interval prolongation is not known, but is presumed to involve abnormal ventricular repolarization and the development of early after‐depolarizations. Before initiating therapy with droperidol or haloperidol in critically ill patients, a baseline QTc interval and serum magnesium and potassium concentrations should be measured. If the baseline QTc interval is 440 msec or longer, and they are receiving other drugs that may prolong the QTc interval or they have electrolyte disturbances, a butyrophenone antipsychotic should be prescribed with caution. All critically ill patients receiving droperidol or haloperidol should undergo electrocardiogram monitoring and QTc interval measurement; special attention should be given to those receiving doses greater than 50 mg/24 hours, as these patients appear to be at greatest risk for development of conduction disturbances. Based on the currently available literature, in any critically ill patient receiving droperidol or haloperidol therapy whose QTc interval lengthens by 25% or more over baseline, therapy should be discontinued or the dosage reduced.