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Background: We have previously demonstrated that tight glycemic control (80-120 mg/dL) improves outcome in critically injured patients. However, many centers have gotten away from aggressive glucose control due to the workload and risk of hypoglycemia. The objective of this pivotal trial is to evaluate the first in human continuous inline glucose monitor (OptiScanner) in critically ill patients., Methods: A multicenter pivotal trial was conducted over a 1-year period (2014-2015) at four major academic centers in 200 critically ill patients. Three thousand seven hundred thirty-five glucose measurements were obtained and measured. A paired blood sample was then collected to coincide with the OptiScan measurement. The OptiScanner withdraws 0.13 mL of blood every 15 minutes from a central venous line, centrifuges the sample, and uses midinfrared spectroscopy to directly measure glucose levels in blood plasma. We plotted a Clarke Error Grid, calculated mean absolute relative difference (MARD) to analyze trend accuracy, and population coefficient of variation (PCV) to measure deviations. OptiScanner and Yellow Springs Instrument values were "blinded" from clinicians. Treatment was guided by the standard point of care meters., Results: 95.4% of the data points were in zone A of the Clarke Error Grid and 4.5% in zone B. The MARD was 7.6%, the PCV 9.6%. The majority of data points achieved the benchmark for accuracy. The MARD was below 10%, which is the first inline continuous glucose monitor to achieve this result in a clinical trial. The PCV was less than 10%. We confirmed that the OptiScanner outperformed every 1- to 3-hour glucose measurements using point of care meters which prevents glucose excursions and variability and achieves a higher amount of time the patient's glucose values remain in range., Conclusion: This pivotal multicenter trial demonstrates that the first inline CGM monitor is safe and accurate for use in critically ill surgical and trauma patients., Level of Evidence: Diagnostic study, level I.

Achieving adequate glucose control in critically ill patients is a complex but important part of optimal patient management. Until relatively recently, intermittent measurements of blood glucose have been the only means of monitoring blood glucose levels. With growing interest in the possible beneficial effects of continuous over intermittent monitoring and the development of several continuous glucose monitoring (CGM) systems, a round table conference was convened to discuss and, where possible, reach consensus on the various aspects related to glucose monitoring and management using these systems. In this report, we discuss the advantages and limitations of the different types of devices available, the potential advantages of continuous over intermittent testing, the relative importance of trend and point accuracy, the standards necessary for reporting results in clinical trials and for recognition by official bodies, and the changes that may be needed in current glucose management protocols as a result of a move towards increased use of CGM. We close with a list of the research priorities in this field, which will be necessary if CGM is to become a routine part of daily practice in the management of critically ill patients.

Current choices for sustained sedation in the critically ill include the benzodiazepines, the opiates, and propofol. Each of these groups of medications has their particular benefits: benzodiazepines provide the greatest amnesia, opiates are the only agents to provide analgesia, and propofol is the most easily titratable and the least likely to excessively accrue. The literature seems to favor propofol over the benzodiazepines as the most cost-effective solution to sustained sedation. A newly approved agent, dexmedetomidine, holds promise as a continuous infusion that can provide both anxiolysis and analgesia, but without the ventilatory depression seen in the other classes of sedatives. Further research is needed to determine the role of dexmedetomidine in the ICU. The emerging standard of care for sustained sedation is the use of standardized protocols, formulated with the help of clinical practice guidelines, and titrated with the guidance of sedation monitoring.

Objective: To describe outcomes of adult survivors of prolonged critical illness after direct transfer to extended care facilities., Design: A retrospective cohort study., Setting: All adult intensive care units (ICUs) in a tertiary care university hospital., Patients: A consecutive series of 97 adult survivors with an ICU stay of > or =7 days transferred directly from intensive care to extended care facilities between 1990 and 1996., Interventions: None., Methods and Main Results: Hospital and extended care facility charts were reviewed for patient characteristics, resource utilization, and survival. Survivors were for a minimum of 1 yr and a maximum of 6 yrs, and were interviewed to assess quality of life and functionality. The mean age of the patients was 66+/-16 (range, 19-93) yrs. The median length of ICU stay for these patients was 39 (range, 7-276) days. Only 18 of the 71 ventilator-assisted patients were weaned from mechanical ventilation after transfer to the extended care facility. Survival for the study period, at 1 yr after discharge from the ICU, was 49.5%. One year after discharge from the ICU, 11.5% of all patients had returned home, were breathing spontaneously, had a fair or better quality of life, and had good physical functionality. Each successive year, an increasing proportion of patients underwent direct transfer to an extended care facility. This strategy decreased the patients' length of stay (p<.002) in the ICU from year to year, but was significantly associated with an increase in readmissions to acute care hospitals (p<.002)., Conclusions: Survivors of catastrophic illness who are so debilitated that they require transfer to an extended care facility have a low likelihood of achieving both survival and functional independence 1 yr after discharge from the ICU. Aggressive cost-conscious strategies to accelerate the transfer of these patients successfully reduced the length of ICU stay and hospital costs, but were associated with a high rate of readmission to tertiary care facilities.

Purpose: The purpose of this study was to investigate the effects of interleukin-1 receptor antagonist (IL-1ra) on myocardial function in septic patients., Materials and Methods: A subgroup of patients from a prospective, randomized, double-blind, placebo-controlled, multicenter trial was studied from 63 academic medical centers in the United States, Canada, and Europe. A subgroup of 71 patients with severe sepsis in whom vasoactive support was little altered during the study was included. The patients were randomized to receive either placebo (n = 29) or IL-1ra at a dose of 1 mg/kg/h (n = 20) or 2 mg/kg/h (n = 22)., Results: Hemodynamic measurements were taken at baseline, and 1, 2, 3, 4, 8, and 12 hours after placebo or IL-1ra administration. No significant differences in hemodynamic parameters were observed between the groups or over time during the study period., Conclusions: IL-1ra administration has no effect on cardiac function in septic patients.

Study Objective: To evaluate gastric alkalization and bacterial colonization in critically ill patients receiving stress ulcer prophylaxis with gastric tube feeds, sucralfate, intermittent intravenous cimetidine, or continuous intravenous cimetidine. DESIGN; Prospective, randomized, unblinded trial., Setting: Medical and surgical intensive care units of a large university-affiliated, tertiary care community hospital., Patients: Fifty-three evaluable critically ill patients with respiratory failure requiring mechanical ventilation., Interventions: Patients not receiving nasogastric tube feeds were randomized to sucralfate 1 g every 6 hours, cimetidine 300 mg by intravenous bolus every 8 hours, or cimetidine 900 mg by continuous intravenous infusion/24 hours. Gastric samples were obtained daily for pH and culture., Measurements and Main Results: Patients with respiratory failure and a high mortality rate had a mean gastric pH of 1.96 +/- 1.5 at study entry. There were no significant differences in gastric pH or gastric colonization among the three arms. Fourteen patients (26%) developed gastric colonization, which was statistically significant but poorly correlated with gastric alkalinity (r2=0.08, p<0.043)., Conclusion: Gastric luminal pH was unchanged regardless of which method was used for stress ulcer prophylaxis. Bacterial colonization was increasingly likely in patients with a persistent alkaline gastric environment.

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 alpha (TNF alpha 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 TNF alpha 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 TNF alpha 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 TNF alpha 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 TNF alpha MAb therapy. Coagulopathy but not other organ or system failures, was significantly decreased in the TNF alpha MAb group compared with placebo (day 7, p<0.001; day 28, p=0.005). Serious adverse events were reported in 55.2% of patients given placebo and 54.1% in the TNF alpha MAb group., Interpretation: We did not find an improvement in survival after septic shock with TNF alpha MAb. Therapy not solely dependent on TNF alpha blockade may be required to improve survival.

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.

The postoperative courses of 115 liver transplant recipients were reviewed to monitor for outcomes of acute renal failure and mortality. An analysis of baseline (preoperative) variables with particular attention to baseline renal function was accomplished to establish predictive variables for a complicated postoperative course. Acute renal failure requiring dialysis occurred in 27 cases (23%) and was associated with a prolonged ICU stay, greater infectious complications, greater hospital charges and a high mortality rate (46 +/- 11% vs. 9 +/- 3%) as compared to patients who did not experience acute renal failure. Death occurred in 20 patients (17%) overall prior to discharge. In order to assess the contribution of renal function, the population was divided arbitrarily into two groups based on preoperative serum creatinine. Group 1 (n = 50) had a preoperative serum creatinine < 1.0 mg/dl (mean +/- SD = 2.2 +/- 0.2 mg/dl) and Group 2 (n = 65) had a preoperative serum creatinine < or = 1.0 mg/dl (0.7 +/- 0.1 mg/dl). The groups experienced similar operative courses. Group 1 patients experienced significantly longer ICU stays (18 +/- 3 vs. 10 +/- 2 days), higher rates of acute renal failure requiring dialysis (52 +/- 7 vs. 5 +/- 2%), higher hospital charges (231,454 +/- 17,088 vs. 178,755 +/- 14,744 $, US) and a greatly increased mortality rate (32 +/- 1 vs. 6 +/- 1%), as compared to Group 2 patients. A multifactorial regression analysis demonstrated that of all pretransplant factors analyzed, elevation in the serum creatinine was significantly associated and was the strongest predictor of both outcomes: acute renal failure requiring dialysis (ROC = 0.89) and death (ROC = 0.83). The presence or absence of hepatorenal syndrome did not influence the results of this analysis. This study demonstrates that cirrhotic patients with renal dysfunction, as indicated by an elevated serum creatinine, experience a poor surgical outcome following liver transplantation. These patients may require special attention in the perioperative period. Alternatively, these data may influence the selection of ideal candidates for liver transplantation, where scarce resources need to be applied appropriately.

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.

Objective: The development of practice parameters for intravenous analgesia and sedation for adult patients in the intensive care unit (ICU) setting for the purpose of guiding clinical practice., Participants: A task force of more than 40 experts in disciplines related to the use of analgesic and sedative agents in the ICU was convened from the membership of the American College of Critical Care Medicine (ACCM) and the Society of Critical Care Medicine (SCCM)., Evidence: The task force members provided the personal experience and determined the published literature (MEDLINE articles, textbooks, pharmacopeias, etc.) from which consensus would be sought. Published literature was reviewed and classified into one of four predetermined categories, according to study design and scientific value., Consensus Process: The task force met several times as a whole, and numerous times in smaller groups by teleconference, over a 1-yr period to identify the pertinent literature and arrive at consensus recommendations for the whole task force to discuss. Consideration was given to the relationship between the weight of scientific information and the experts' viewpoints. Over the next year, draft documents were composed by a task force steering committee and debated by the task force members until consensus was reached by nominal group process. The task force draft was then reviewed, assessed, and edited by the Board of Regents of the ACCM. After steering committee approval, the draft document was reviewed and approved by the SCCM Council., Data Synthesis: To facilitate rapid communication of the six recommendations contained within the complete and unabridged practice parameter document, an executive summary was prepared for publication by the ACCM Board of Regents, and this executive summary was approved by the task force steering committee and the SCCM Executive Council., Conclusions: A consensus of experts provided six recommendations with supporting data for intravenous analgesia and sedation in the ICU setting: a) morphine sulfate is the preferred analgesic agent for critically ill patients; b) fentanyl is the preferred analgesic agent for critically ill patients with hemodynamic instability, for patients manifesting symptoms of histamine release with morphine, or morphine allergy; c) hydromorphone can serve as an acceptable alternative to morphine; d) midazolam or propofol are the preferred agents only for the short-term (< 24 hrs) treatment of anxiety in the critically ill adult; e) lorazepam is the preferred agent for the prolonged treatment of anxiety in the critically ill adult; f) haloperidol is the preferred agent for the treatment of delirium in the critically ill adult. This executive summary selectively presents supporting information and is not intended as a substitute for the complete document.

Objective: The development of practice parameters for achieving sustained neuromuscular blockade in the adult critically ill patient for the purpose of guiding clinical practice., Participants: A task force of more than 40 experts in disciplines related to the use of neuromuscular blocking agents in the intensive care unit was convened from the membership of the American College of Critical Care Medicine (ACCM) and the Society of Critical Care Medicine (SCCM)., Evidence: The task force members provided the personal experience and determined the published literature (MEDLINE articles, textbooks, pharmacopeias, etc.) from which consensus would be sought. Published literature was reviewed and classified into one of four predetermined categories, according to study design and scientific value., Consensus Process: The task force met several times as a whole, and numerous times in smaller groups by teleconference, over a 1-yr period to identify the pertinent literature and arrive at consensus recommendations for the whole task force to discuss. Consideration was given to the relationship between the weight of scientific information and the experts' viewpoints. Over the next year, draft documents were composed by a task force steering committee and debated by the task force members until consensus was reached by nominal group process. The task force draft was then reviewed, assessed, and edited by the Board of Regents of the ACCM. After steering committee approval, the draft document was reviewed and approved by the SCCM Council., Data Synthesis: To facilitate rapid communication of the three recommendations contained within the complete and unabridged practice parameter document, an executive summary was prepared for publication by the ACCM Board of Regents, and this executive summary was approved by the task force steering committee and the SCCM Executive Council., Conclusions: A consensus of experts provided three recommendations with supporting data for achieving sustained neuromuscular blockade in critically ill patients: a) pancuronium is the preferred neuromuscular blocking agent for most critically ill patients; b) vecuronium is the preferred neuromuscular blocking agent for those patients with cardiac disease or hemodynamic instability in whom tachycardia may be deleterious; c) patients receiving neuromuscular blocking agents should be appropriately assessed for the degree of blockade that is being sustained. This executive summary selectively presents supporting information and is not intended as a substitute for the complete document.

Objective: To evaluate the efficacy and safety of anti-tumor necrosis factor alpha monoclonal antibody (TNF-alpha MAb) in the treatment of patients with sepsis syndrome., Design: Randomized, prospective, multicenter, double-blind, placebo-controlled clinical trial., Setting: A total of 31 hospitals in the United States and Canada., Patients: There were 994 patients with sepsis syndrome enrolled in this clinical trial, and 971 patients were infused with the study drug., Intervention: Patients were prospectively stratified into shock or nonshock groups and then randomized to receive a single infusion of 15 mg/kg of TNF-alpha MAb, 7.5 mg/kg of TNF-alpha MAb, or placebo. Patients received standard aggressive medical and surgical care during the 28-day postinfusion period., Outcome Measure: Twenty-eight-day all-cause mortality., Results: The distribution of variables describing demographics, organ system dysfunction or failure, preinfusion Acute Physiology and Chronic Health Evaluation II score, number of organs failing at baseline, initial sites of infection, infecting microorganisms, antimicrobials used, and initial invasive procedures was similar among patients in the TNF-alpha MAb and placebo treatment arms. Among all infused patients, there was no difference in all-cause mortality in patients who received placebo as compared with those who received TNF-alpha MAb. In septic patients with shock (n = 478), there was a trend toward a reduction in all-cause mortality, which was most evident 3 days after infusion: 25 of 162 patients treated with 15 mg/kg of TNF-alpha MAb died, 22 of 156 patients treated with 7.5 mg/kg of TNF-alpha MAb died, and 44 of 160 patients in the placebo group died (15 mg/kg: 44% reduction vs placebo, P = .01; 7.5 mg/kg: 48.7% reduction vs placebo, P = .004). At day 28, the reduction in mortality for shock patients was not significant for either dose of TNF-alpha MAb relative to placebo (15 mg/kg, 61 deaths among 162 patients [37.7% mortality]; 7.5 mg/kg, 59 deaths among 156 patients [37.8% mortality]; placebo, 73 deaths among 160 patients [45.6% mortality]; P = .20 for 7.5 mg/kg and P = .15 for 15 mg/kg). Serious adverse events were reported in 4.6% of all infused patients. No immediate hypersensitivity allergic reactions due to TNF-alpha MAb were reported. Serum sickness-like reactions were seen in 2.5% of patients receiving TNF-alpha MAb., Conclusions: There was no decrease in mortality between placebo and TNF-alpha MAb in all infused patients. In septic shock patients who received TNF-alpha MAb, a significant reduction in mortality was present 3 days after infusion. Although a trend toward reduced mortality continued at 28 days following treatment with TNF-alpha MAb, the difference in mortality among shock patients treated with placebo or TNF-alpha MAb was not significant.

Objective: To examine the effect of multiple organ failure after liver transplantation on mortality and resource utilization., Design: Retrospective cohort study., Setting: Surgical intensive care unit in a tertiary care university hospital., Patients: Consecutive series of 113 adults undergoing liver transplantation between 1984 and 1992. Patients were excluded if they died intraoperatively (n = 2), required retransplantation (n = 8), or had incomplete records (n = 7)., Interventions: None., Measurements and Main Results: We prospectively developed definitions for organ failure, and quantitated the frequency and related outcomes for mortality and resource utilization. Multiple organ failure was defined as the presence of two or more organ failures. Patients were grouped according to the presence (n = 31) or absence (n = 65) of multiple organ failure. Preoperative severity of illness was assessed by the Acute Physiology and Chronic Health Evaluation (APACHE II) and United Network for Organ Sharing (UNOS) scoring systems. Postoperative outcome data, including hospital survival rate, hospital length of stay, and charges were recorded. The frequency of multiple organ failure after liver transplantation was 32%. The mortality rate in the patients who developed multiple organ failure was 42% vs. only 2% in those patients without multiple organ failure (p < .0001). Patients with four or more organ failures had a 100% mortality rate. Postoperative multiple organ failure was associated with increased hospital length of stay (46 +/- 7 days vs. 29 +/- 2 days; p = .026) and increased hospital charges ($271,497 +/- 29,994 vs. $136,372 +/- 8,310; p < .0001). Higher preoperative APACHE II and UNOS scores predicted postoperative multiple organ failure, but were less accurate tools for predicting risk of death., Conclusions: Multiple organ failure is associated with death and increased resource utilization in liver transplantation. Pretransplantation severity of illness, as measured by APACHE II and UNOS scoring systems, is an important determinant of postoperative multiple organ failure and outcome.

Objective: To describe the hemodynamic and oxygen transport patterns in survivors and nonsurvivors following liver transplantation (LT) and to assess their relationship to organ failure and mortality., Design: Retrospective cohort., Setting: Surgical ICU in a tertiary care university teaching hospital., Patients: Consecutive series of 113 adults undergoing LT between 1984 and 1992. Patients were excluded if they died intraoperatively (n = 2), required retransplantation (n = 8), or their records were incomplete (n = 7)., Measurements and Main Results: Preoperative severity of illness was assessed by the acute physiology and chronic health evaluation (APACHE) II scoring system. Hemodynamic and oxygen transport variables were recorded immediately preoperatively and sequentially every 12 h during the first 2 postoperative days. Organ failures (pulmonary, renal, cardiovascular, hepatic, and central nervous system) were assessed for patients in the postoperative period. Patients were grouped as survivors (n = 82) or nonsurvivors (n = 14) with a mortality rate of 15%. Preoperative APACHE II scores were significantly lower in survivors compared with nonsurvivors (7 +/- 0 vs 11 +/- 2; p = 0.029). Both preoperatively and postoperatively, survivors sustained a relatively higher mean arterial pressure, stroke volume index, left ventricular stroke work index, cardiac index, and oxygen delivery as compared with nonsurvivors (p < 0.01). The postoperative decline in systemic blood flow that was seen in both groups was particularly prominent in nonsurvivors during the first 12 h following LT (p < 0.03). Nonsurvivors sustained an approximately fivefold increase in the rate of organ failure (p < 0.0001); all patients (n = 6) with 4 or more organ failures died., Conclusion: Nonsurvivors of LT have less cardiac reserve pretransplant; postoperatively, they demonstrate early myocardial depression and subsequently lower levels of cardiac index and oxygen delivery. Patients who develop these hemodynamic patterns are more prone to organ failure and death.

Life-threatening acute pulmonary embolism (PE) associated with circulatory shock requires effective therapy directed at removing the obstruction to flow in the pulmonary vasculature and improving hemodynamics. Options for treatment are pulmonary embolectomy and thrombolytic therapy. Although safe and effective, thrombolytic therapy is relatively contraindicated within 10 days of major surgery due to the risk of bleeding. Intravenous streptokinase was administered to a man on the third postoperative day for treatment of a massive PE associated with circulatory shock. Within 2 hours of initiating therapy, the patient experienced marked improvement in hemodynamics and tissue perfusion. No bleeding complications were noted. This case demonstrates that intravenous thrombolytics may be administered safely to patients who have recently undergone surgery. It also underscores that the decision to apply the therapy when relatively contraindicated must be made on an individual patient basis and thus ensure that potentially life-saving therapy is not withheld from those who require it most.

As the population ages and as surgical and anesthetic techniques advance, more and more elderly patients are referred for surgery. As a result, the physician must be increasingly aware of the aged response to surgery and the management of the geriatric surgical patient in the perioperative period. Elderly patients are prone to cardiac, respiratory, and infectious complications, and thus, they need to be screened for the presence of pre-existing disease. In addition, the geriatric patient needs to be carefully monitored in the proper postoperative environment to guard against untoward sequelae.

We studied the inotropic response to dopamine and digoxin in 20 patients with severe sepsis and left ventricular failure. Left ventricular failure was defined as a left ventricular stroke work index less than or equal to 40 g.m/m2 at a pulmonary artery wedge pressure greater than or equal to 15 mm Hg. Hemodynamic assessment was obtained before and following administration of digoxin 10 micrograms/kg IV or dopamine, 5 to 12 micrograms/kg/min IV. Patients treated with digoxin demonstrated a significant increase in LVSWI. The LVSWI increased 13 +/- 10 percent in the dopamine-treated patients compared with 74 +/- 16 percent in the digoxin patients (p less than 0.02). We conclude that digoxin exhibited significant inotropic activity in patients with sepsis.