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.

Use of sedative medications in the intensive care unit.

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.

Survivors of catastrophic illness: outcome after direct transfer from intensive care to extended care facilities.

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.

Gastric colonization as a consequence of stress ulcer prophylaxis: a prospective, randomized trial.

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.

Guidelines on admission and discharge for adult intermediate care units. American College of Critical Care Medicine of the Society of Critical Care Medicine.

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.

Pretransplant renal dysfunction predicts poorer outcome in liver transplantation.

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.

Concepts of fever: recent advances and lingering dogma.

Fever has been a preoccupation of clinicians since medicine's beginning. One might therefore expect that basic concepts relating to this physiological response would be well delineated and that such concepts would be widely known. In fact, only in the past several decades has the febrile response been subjected to scientific scrutiny. As a result of recent scientific investigation, modern concepts have evolved from a perception of fever as nothing more than a rise in core temperature to one in which fever is recognized as a complex physiological response characterized by a cytokine-mediated rise in temperature, as well as by generation of acute-phase reactants and activation of a panoply of physiological, endocrinologic, and immunologic systems. The average clinician appears to have little more than a regrettably rudimentary knowledge of these modern concepts of fever. This symposium summary considers many such concepts that have immediate relevance to the practice of medicine.

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.

Practice parameters for intravenous analgesia and sedation for adult patients in the intensive care unit: an executive summary. Society of Critical Care Medicine.

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.

Practice parameters for sustained neuromuscular blockade in the adult critically ill patient: an executive summary. Society of Critical Care Medicine.

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.

Multiple organ failure after liver transplantation.

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.

Hemodynamic correlates of outcome in patients undergoing orthotopic liver transplantation. Evidence for early postoperative myocardial depression.

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.

Thrombolytic therapy for pulmonary embolism: reversal of shock in the early postoperative period.

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.

Preoperative evaluation and postoperative care of the elderly patient undergoing major surgery.

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.