Douglas B. Coursin

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

Clinical Practice Guidelines for the Management of Pain, Agitation, and Delirium in Adult Patients in the Intensive Care Unit

Objective:To revise the “Clinical Practice Guidelines for the Sustained Use of Sedatives and Analgesics in the Critically Ill Adult” published in Critical Care Medicine in 2002. Methods:The American College of Critical Care Medicine assembled a 20-person, multidisciplinary, multi-institutional task force with expertise in guideline development, pain, agitation and sedation, delirium management, and associated outcomes in adult critically ill patients. The task force, divided into four subcommittees, collaborated over 6 yr in person, via teleconferences, and via electronic communication. Subcommittees were responsible for developing relevant clinical questions, using the Grading of Recommendations Assessment, Development and Evaluation method (http://www.gradeworkinggroup.org) to review, evaluate, and summarize the literature, and to develop clinical statements (descriptive) and recommendations (actionable). With the help of a professional librarian and Refworks® database software, they developed a Web-based electronic database of over 19,000 references extracted from eight clinical search engines, related to pain and analgesia, agitation and sedation, delirium, and related clinical outcomes in adult ICU patients. The group also used psychometric analyses to evaluate and compare pain, agitation/sedation, and delirium assessment tools. All task force members were allowed to review the literature supporting each statement and recommendation and provided feedback to the subcommittees. Group consensus was achieved for all statements and recommendations using the nominal group technique and the modified Delphi method, with anonymous voting by all task force members using E-Survey (http://www.esurvey.com). All voting was completed in December 2010. Relevant studies published after this date and prior to publication of these guidelines were referenced in the text. The quality of evidence for each statement and recommendation was ranked as high (A), moderate (B), or low/very low (C). The strength of recommendations was ranked as strong (1) or weak (2), and either in favor of (+) or against (–) an intervention. A strong recommendation (either for or against) indicated that the intervention’s desirable effects either clearly outweighed its undesirable effects (risks, burdens, and costs) or it did not. For all strong recommendations, the phrase “We recommend …” is used throughout. A weak recommendation, either for or against an intervention, indicated that the trade-off between desirable and undesirable effects was less clear. For all weak recommendations, the phrase “We suggest …” is used throughout. In the absence of sufficient evidence, or when group consensus could not be achieved, no recommendation (0) was made. Consensus based on expert opinion was not used as a substitute for a lack of evidence. A consistent method for addressing potential conflict of interest was followed if task force members were coauthors of related research. The development of this guideline was independent of any industry funding. Conclusion:These guidelines provide a roadmap for developing integrated, evidence-based, and patient-centered protocols for preventing and treating pain, agitation, and delirium in critically ill patients.

Glucose control in the intensive care unit.

Objective:Hyperglycemia, be it secondary to diabetes, impaired glucose tolerance, impaired fasting glucose, or stress-induced is common in the critically ill. Hyperglycemia and glucose variability in intensive care unit (ICU) patients has some experts calling for routine administration of intensive insulin therapy to normalize glucose levels in hyperglycemic patients. Others, however, have raised concerns over the optimal glucose level, the accuracy of measurements, the resources required to attain tight glycemic control (TGC), and the impact of TGC across the heterogeneous ICU population in patients with diabetes, previously undiagnosed diabetes or stress-induced hyperglycemia. Increased variability in glucose levels during critical illness and the therapeutic intervention thereof have recently been reported to have a deleterious impact on survival, particularly in nondiabetic hyperglycemic patients. The incidence of hypoglycemia (<40 mg/dL or 2.2 mmol) associated with TGC is reported to be as high as 18.7%, by Van den Berghe in a medical ICU, although application of various approaches and computer-based algorithms may improve this. The impact of hypoglycemia, particularly in patients with septic shock and those with neurologic compromise, warrants further evaluation. This review briefly discusses the epidemiology of hyperglycemia in the acutely ill and glucose metabolism in the critically ill. It comments on present limitations in glucose monitoring, outlines current glucose management approaches in the critically ill, and the transition from the ICU to the intermediate care unit or ward. It closes with comment on future developments in glycemic care of the critically ill. Methods:The awareness of the potential deleterious impact of hyperglycemia was heightened after Van den Berghe et al presented their prospective trial in 2001. Therefore, source data were obtained from PubMed and Cochrane Analysis searches of the medical literature, with emphasis on the time period after 2000. Recent meta-analyses were reviewed, expert editorial opinion collated, and the Web site of the Normoglycemia in Intensive Care Evaluation and Survival Using Glucose Algorithm Regulation Trial investigated. Summary and Conclusions:Hyperglycemia develops commonly in the critically ill and impacts outcome in patients with diabetes but, even more so, in patients with stress-induced hyperglycemia. Despite calls for TGC by various experts and regulatory agencies, supporting data remain somewhat incomplete and conflicting. A recently completed large international study, Normoglycemia in Intensive Care Evaluation and Survival Using Glucose Algorithm Regulation, should provide information to further guide best practice. This concise review interprets the current state of adult glycemic management guidelines to provide a template for care as new information becomes available.

Perioperative care of the liver transplant patient: Part 1.

erioperative care of the patient undergoing liver transplantation or retransplantation is one of P the most challenging clinical situations that the surgeon, anesthesiologist, and critical care physician currently encounter (1). Liver transplantation has evolved dramatically during the past decade, driven by the availability of more specific immunosuppressive drugs (most notably cyclosporine and monoclonal antibody therapy), improved surgical and medical techniques, and the development of an enhanced organ preservation solution. Orthotopic liver transplantation (OLT) refers to liver transplantation after removal of the diseased recipient liver. There are currently nearly 70 medical centers that perform approximately 2,500 liver transplantations annually in the United States alone. Starzl et al. who performed the first clinical liver transplant in November, 1963, has projected that between 4,000 and 50,000 liver transplantations a year may be needed in the United States if sufficient donors are available (1). The patient being considered for liver transplantation requires a thorough individual preoperative evaluation and the support of multiple physicians and ancillary services with a meticulous approach to the evaluation process. The rate of deterioration of liver function is highly variable, but patients frequently present for urgent OLT with severe single or multiple end-organ dysfunction. This two-part review will focus on the preoperative assessment, the intraoperative management, and the acute postoperative course of patients presenting for OLT. It will emphasize the collective experience of several major medical centers and the personal experience of the authors who actively care for liver transplant patients at two institutions.

Comparison of the Infusion Requirements and Recovery Profiles of Vecuronium and Cisatracurium 51W89 in Intensive Care Unit Patients

The selection and administration of neuromuscular blocking (NMB) drugs in intensive care unit (ICU) patients remain controversial.We compared the dose-response and recovery pharmacodynamics of a new intermediate-acting NMB drug, cisatracurium besylate, to the intermediate-acting NMB drug, vecuronium (VEC), in a prospective, randomized, double-blind, multicenter study in critically ill adults. After informed consent, 58 mechanically ventilated ICU patients from five medical centers were randomized to receive either cisatracurium or VEC. Fifty-four of the 58 patients received NMB drugs before entering this study but demonstrated at least partial recovery (>or=to one twitch) in the train-of-four (TOF) response before initiation of the NMB study drug. NMB drug infusion was titrated by peripheral nerve stimulation to maintain at least one twitch in the TOF response. NMB drugs were infused for 1-5 days. After discontinuation of NMB drug infusion, recovery of neuromuscular transmission was monitored with an accelerometer. NMB drug infusion for 28 cisatracurium patients averaged 2.6 +/- 0.2 (mean +/- SEM) micro gram centered dot kg-1 centered dot min-1 with a mean duration of 80 +/- 7 h. After discontinuing cisatracurium administration, recovery to 70% TOF ratio averaged 68 +/- 13 min. The mean infusion rate for 30 VEC patients was 0.9 +/- 0.1 micro gram centered dot kg-1 centered dot min-1 with a mean duration of 66 +/- 12 h. Neuromuscular recovery after VEC averaged 387 +/- 163 min, which was significantly longer (P = 0.02) than that after cisatracurium. Prolonged recovery of neuromuscular function after discontinuation of NMB drug infusion (identified by the primary investigator at each medical center) was reported in two cisatracurium patients and 13 VEC patients (P = 0.002), and occurred despite the routine use of neuromuscular twitch monitoring. Seven VEC and one cisatracurium patients died during the infusion of study drug or within 48 h after discontinuation of the NMB drug infusion. In summary, we found recovery of neuromuscular function after discontinuation of NMB drug infusion in ICU patients is significantly faster with cisatracurium than with VEC. In addition, routine neuromuscular monitoring was not sufficient to eliminate prolonged recovery and myopathy in ICU patients. (Anesth Analg 1995;81:3-12)

A national survey on the practice patterns of anesthesiologist intensivists in the use of muscle relaxants

ConclusionsThis study was created to address the dearth of information regarding actual usage of muscle relaxants in the ICU setting. The survey population was chosen as one with great familiarity in the use of muscle relaxants. The 55% response rate was significantly greater than the expected response rate for a single mailing survey. In the ICU setting, neuromuscular blocking drugs are most frequently used to facilitate mechanical ventilation. The prevalence of vecu-ronium use is of interest in light of recent case reports of prolonged neuromuscular blockade after long-term vecuronium administration. The low frequency of peripheral nerve stimulator monitoring during muscle relaxation may contribute, in part, to the problem of prolonged blockade after drug withdrawal. Muscle relaxants are not used in the absence of sedation and/ or analgesia by this practitioner population. (Crit Care Med 1992; 20:1341–1345)

Prolonged weakness after infusion of atracurium in two intensive care unit patients.

dministration of neuromuscular blocking (NMB) drugs to patients in the intensive care A unit (ICU) is used to facilitate mechanical ventilation, control intracranial hypertension, eliminate shivering, decrease oxygen consumption, and facilitate diagnostic procedures and studies (1,2). In the United States, the steroid-based NMB drugs, vecuronium and pancuronium, are most frequently selected for ICU administration (1,2). However, numerous reports suggest that prolonged administration of these drugs to ICU patients may result in sustained weakness, persisting days to weeks after withdrawal of the drug (3-5). Three features are common to these reports: 1) the prolonged, usually continuous infusion of steroid-based NMB agents, most often without peripheral nerve twitch monitoring, 2) concurrent administration of drugs which may alter neuromuscular transmission such as aminoglycoside antibiotics, calcium-channel blockers, magnesium, and especially high-dose corticosteroids, and 3 ) end-organ dysfunction such as significant renal failure (3-11). Because of concern about administration of steroidbased NMB drugs in patients receiving concurrent exogenous corticosteroids, recommended strategies include the use of routine peripheral nerve twitch monitoring and the selection of neuromuscular blocking agents with an alternative (nonsteroid) pharmacologic structure (12). Atracurium, an intermediate-acting benzylisoquinolinium compound, is structurally unrelated to the aminosteroid NMB agents (13). Introduced in 1983, atracurium is a unique NMB drug that undergoes ester hydrolysis and Hofmann elimination (independent of hepatic or renal function) to laudanosine and monoacrylate metabolites (131, which are inactive at the neuromuscular junction.

Review article: glucose measurement in the operating room: more complicated than it seems.

Abnormalities of blood glucose are common in patients undergoing surgery, and in recent years there has been considerable interest in tight control of glucose in the perioperative period. Implementation of any regime of close glycemic control requires more frequent measurement of blood glucose, a function for which small, inexpensive, and rapidly responding point-of-care devices might seem highly suitable. However, what is not well understood by many anesthesiologists and other staff caring for patients in the perioperative period is the lack of accuracy of home glucose meters that were designed for self-monitoring of blood glucose by patients. These devices have been remarketed to hospitals without appropriate additional testing and without an appropriate regulatory framework. Clinicians who are accustomed to the high level of accuracy of glucose measurement by a central laboratory device or by an automated blood gas analyzer may be unaware of the potential for harmful clinical errors that are caused by the inaccuracy exhibited by many self-monitoring of blood glucose devices, especially in the hypoglycemic range. Knowledge of the limitations of these meters is essential for the perioperative physician to minimize the possibility of a harmful measurement error. In this article, we will highlight these areas of interest and review the indications, technology, accuracy, and regulation of glucose measurement devices used in the perioperative setting.

Assessment and therapy of selected endocrine disorders

Diabetes remains the most commonly encountered endocrinopathy with the incidence of type 2 doubling in the past decade. The prevalence of diabetes is projected to continue to increase dramatically over the next several decades unless major public health initiatives are successful in stemming this growth. Both type I and 2 diabetics more frequently require surgical and critical care than their non-diabetic counterparts. Type 1 and 2 diabetics also sustain greater peri-operative morbidity and mortality. Careful preoperative assessment and appropriate perioperative intervention may limit this. There is increasing evidence that maintenance of normal blood glucose in the perioperative period and during critical illness is beneficial for diabetic and non-diabetic patients. More data will hopefully be forthcoming to substantiate recent reports and identify the mechanisms of improved outcome. Thyroid disease remains a commonly encountered pathology that is more readily identified and controlled in the modern era of radioimmune assays of thyroid hormone and successful medical and surgical therapies. Severe hypothyroidism and thyroid storm are associated with significant increases in perioperative morbidity and mortality. Recognition of these entities or those at risk for developing them post operatively is crucial in initiating timely and effective therapy. Primary Al is uncommon, but results in glucocorticoid and mineralocorticoid deficiency. Tertiary Al is far more common, most often secondary to iatrogenic therapy with exogenous glucocorticoids for the management of chronic diseases such as connective tissue disorders, anti-rejection regimes, and severe asthma. Glucocorticoid replacement or supplementation is needed on a case-by-case basis and should be individualized based on chronic steroid dose, duration, and stress of the surgical procedure. Perioperative steroid dosing regimes now recommend lower doses for shorter periods than previously suggested. More recently Al has been recognized in two populations, elderly patients undergoing major surgery and a subgroup of patients with septic shock. Timely diagnosis using synthetic ACTH stimulation testing and stress glucocorticoid, and possibly mineralocorticoid therapy, seems to reverse these processes and improve recovery. Although uncommon, patients with pheochromocytoma who undergo open or laparoscopic resections remain diagnostic and therapeutic challenges. Perioperative outcome seems to have improved, in part, related to newer therapies and less invasive surgeries when indicated. The appropriate preoperative assessment and management of patients with various endocrinopathies is important to optimize outcome and limit avoidable complications. Hopefully additional evidence based guidelines will be forth-coming particularly in caring for the ever increasingly encountered perioperative diabetic.

Critical glucose control: the devil is in the details.

This issue of Mayo Clinic Proceedings contains 3 articles on maintaining normal glucose levels in hospitalized patients. 1-3 The report by Desachy et al 1 ddresses a concept—reliably measuring glucose in critically ill patients—that is important to understanding the other 2 articles. The accuracy of point-of-care (POC) glucometers and variability of glucose measurement in the intensive care unit (ICU) are where the details meet the devil. 1 The potential effect of inaccurate glucose measurements on tight glycemic control (TGC) protocols using intensive insulin therapy (IIT) must be appreciated. Variability in measurement technique and results could explain some of the conflicting opinions about the advisability of aggressive control of glucose levels in critically ill patients. 4,5