Greg Schumaker

Incidence of propofol-related infusion syndrome in critically ill adults: a prospective, multicenter study

IntroductionWhile propofol is associated with an infusion syndrome (PRIS) that may cause death, the incidence of PRIS is unknown. Determining the incidence of PRIS and the frequency of PRIS-related clinical manifestations are key steps prior to the completion of any controlled studies investigating PRIS. This prospective, multicenter study sought to determine the incidence of PRIS and PRIS-related clinical manifestations in a large cohort of critically ill adults prescribed propofol.MethodsCritically ill adults from 11 academic medical centers administered an infusion of propofol for [>/=] 24 hours were monitored at baseline and then on a daily basis until propofol was discontinued for the presence of 11 different PRIS-associated clinical manifestations and risk factors derived from 83 published case reports of PRIS.ResultsAmong 1017 patients [medical (35%), neurosurgical (25%)], PRIS (defined as metabolic acidosis plus cardiac dysfunction and [>/=] 1 of: rhabdomyolysis, hypertriglyceridemia or renal failure occurring after the start of propofol therapy) developed in 11 (1.1%) patients an average of 3 (1-6) [median (range)] days after the start of propofol. While most (91%) of the patients who developed PRIS were receiving a vasopressor (80% initiated after the start of propofol therapy), few received a propofol dose >83 mcg/kg/min (18%) or died (18%). Compared to the 1006 patients who did not develop PRIS, the APACHE II score (25 +/- 6 vs 20 +/- 7, P = 0.01) was greater in patients with PRIS but both the duration of propofol use (P = 0.43) and ICU length of stay (P = 0.82) were similar.ConclusionsDespite using a conservative definition for PRIS, and only considering new-onset PRIS clinical manifestations, the incidence of PRIS slightly exceeds 1%. Future controlled studies focusing on evaluating whether propofol manifests the derangements of critical illness more frequently than other sedatives will need to be large. These studies should also investigate the mechanism(s) and risk factors for PRIS.

Predictors of mortality in patients with suspected propofol infusion syndrome

Objectives:To identify predictors of mortality in patients with suspected propofol infusion syndrome and to develop a simple scoring system to identify patients with suspected propofol infusion syndrome who are most at risk of death. Design:Retrospective, database analysis. Setting:MEDWATCH system. Participants:Reports (1989–2005) where propofol was associated with ≥1 of 24 published propofol infusion syndrome clinical manifestations. Interventions:None. Measurements and Main Results:After comparison of demographic and clinical manifestations between survivors and nonsurvivors, a multivariate logistic regression model was built through a stepwise selection process and then used to develop a simplified mortality scoring system. Of 1139 patients with suspected propofol infusion syndrome, 342 (30%) were fatal. Death was more likely if patients were ≤18 yrs (odds ratio [95% confidence interval], 2.3 [1.7–3.2]), male (1.3 [1.1–1.7]), received a vasopressor (1.8 [1.3–2.5)]), or had the following clinical manifestations: cardiac (3.8 [2.88–4.91]), metabolic acidosis (3.7 [2.7–5.0]), renal failure (1.9 [1.4–2.6]), hypotension (1.8 [1.3–2.3]), rhabdomyolysis (1.8 [1.3–2.3]), or dyslipidemia (2.0 [1.2–3.4]). The multivariable modeling process found that cardiac symptoms, rhabdomyolosis, hypotension, metabolic acidosis, renal failure, and age each affected survival, although significant interactions existed between some of these factors. Based on the combination of the presence or absence of the six factors in the multivariate model, a propofol infusion syndrome mortality risk score of 0 to 4 resulted in a predicted %/observed % mortality for each score of 0 (10%/10%), 1 (24%/24%), 2 (47%/44%), 3 (72%/81%), and 4 (89%/83%). Conclusions:A number of characteristics are independently associated with higher mortality in patients with suspected propofol infusion syndrome, only some of which are currently reflected in the package insert. Further research should focus on prospectively evaluating the mortality scoring system in patients with suspected propofol infusion syndrome.

Use of a validated delirium assessment tool improves the ability of physicians to identify delirium in medical intensive care unit patients

Objective: Although medical intensive care unit nurses at our institution routinely use the Intensive Care Delirium Screening Checklist (ICDSC) to identify delirium, physicians rely on traditional diagnostic methods. We sought to measure the effect of physicians’ use of the ICDSC on their ability to detect delirium. Design: Before–after study. Setting: Medical intensive care unit of an academic medical center Patients and Participants: A total of 25 physicians with >=1 month of clinical experience in the medical intensive care unit conducted 300 delirium assessments in 100 medical intensive care unit patients. Measurements and Main Results: Physicians sequentially evaluated two patients for delirium using whatever diagnostic method preferred. Following standardized education regarding ICDSC use, each physician evaluated two different patients for delirium using the ICDSC. Each physician assessment was preceded by consecutive, but independent, evaluations for delirium by the patients nurse and then a validated judge using the ICDSC. Before (PRE) physician ICDSC use, the validated judge identified delirium in five patients; the physicians and nurses identified delirium in zero and four of these patients, respectively. The physicians incorrectly identified delirium in four additional patients. After (POST) physician ICDSC use, the validated judge identified delirium in 11 patients; the physicians and nurses identified delirium in eight and ten of these patients, respectively. The physicians incorrectly identified delirium in one patient. After physician ICDSC use, agreement improved between both the physicians and validated judge (PRE [kappa] = ‐0.14 [95% confidence interval {CI} = ‐0.27 to ‐0.02] to POST [kappa] = 0.67 [95% CI = 0.38 to 0.96]) and physicians and nurses (PRE [kappa] = ‐0.15 [95% CI = ‐0.29 to ‐0.02] to POST [kappa] = 0.58 [95% CI = 0.25 to 0.91]). Nurses vs. validated judge agreement was strong in both periods (PRE [kappa] = 0.65 [95% CI = 0.29 to 1.00] and POST [kappa] = 0.92 [95% CI = 0.76 to 1.00]). Conclusions: Use of the ICDSC, along with education supporting its use, improves the ability of physicians to detect delirium in the medical intensive care unit.

Reduced respiratory and skeletal muscle strength in survivors of sibling or unrelated donor hematopoietic stem cell transplantation

We performed a retrospective analysis of muscle strength testing obtained following sibling or unrelated donor hematopoietic stem cell transplant (HSCT) between 1 January 1999 and 31 December 2003 in a cohort of 44 subjects at Tufts-New England Medical Center. Maximal inspiratory pressure (PImax) was ⩽80% predicted in 52% of subjects and ⩽60% predicted in 20% of subjects; maximal expiratory pressure (PEmax) was ⩽80% predicted in 88% of subjects and ⩽60% predicted in 74% of subjects. Patients with a PImax ⩽60% predicted spent significantly longer time in hospital following HSCT compared with subjects with PImax 60% predicted. Grip strength (n=32) was reduced to ⩽80% predicted in 75% of subjects and ⩽60% predicted in 47% of subjects following HSCT. Analysis of paired measurements obtained before and after HSCT in 20 of the 44 subjects (45%) showed significant reduction in both PImax and PEmax between the two measures. Respiratory and skeletal muscle weakness is present in a significant percentage of subjects undergoing pulmonary function testing in the post-HSCT period, and may contribute to pulmonary morbidity in subjects with pulmonary complications of HSCT.

Preventing ICU Subsyndromal Delirium Conversion to Delirium With Low-Dose IV Haloperidol: A Double-Blind, Placebo-Controlled Pilot Study.

Objective:To compare the efficacy and safety of scheduled low-dose haloperidol versus placebo for the prevention of delirium (Intensive Care Delirium Screening Checklist ≥ 4) administered to critically ill adults with subsyndromal delirium (Intensive Care Delirium Screening Checklist = 1–3). Design:Randomized, double-blind, placebo-controlled trial. Setting:Three 10-bed ICUs (two medical and one surgical) at an academic medical center in the United States. Patients:Sixty-eight mechanically ventilated patients with subsyndromal delirium without complicating neurologic conditions, cardiac surgery, or requiring deep sedation. Interventions:Patients were randomly assigned to receive IV haloperidol 1 mg or placebo every 6 hours until delirium occurred (Intensive Care Delirium Screening Checklist ≥ 4 with psychiatric confirmation), 10 days of therapy had elapsed, or ICU discharge. Measurements and Main Results:Baseline characteristics were similar between the haloperidol (n = 34) and placebo (n = 34) groups. A similar number of patients given haloperidol (12/34 [35%]) and placebo (8/34 [23%]) developed delirium (p = 0.29). Haloperidol use reduced the hours per study day spent agitated (Sedation Agitation Scale ≥ 5) (p = 0.008), but it did not influence the proportion of 12-hour ICU shifts patients spent alive without coma (Sedation Agitation Scale ⩽ 2) or delirium (p = 0.36), the time to first delirium occurrence (p = 0.22), nor delirium duration (p = 0.26). Days of mechanical ventilation (p = 0.80), ICU mortality (p = 0.55), and ICU patient disposition (p = 0.22) were similar in the two groups. The proportion of patients who developed corrected QT-interval prolongation (p = 0.16), extrapyramidal symptoms (p = 0.31), excessive sedation (p = 0.31), or new-onset hypotension (p = 1.0) that resulted in study drug discontinuation was comparable between the two groups. Conclusions:Low-dose scheduled haloperidol, initiated early in the ICU stay, does not prevent delirium and has little therapeutic advantage in mechanically ventilated, critically ill adults with subsyndromal delirium.

Sleep and Mechanical Ventilation

Critically ill patients have severe sleep disruption and typically encounter loss of circadian sleep pattern, steep fragmentation, increasing proportions of transitional stages of sleep, and loss of slow wave and rapid eye movement sleep. Mechanical ventilation is associated with these same sleep abnormalities, but what is attributable to the intensive care unit environment versus mechanical ventilation itself may be difficult to discern. Recent studies have shown that the ventilator mode and inappropriate settings can contribute to sleep fragmentation, and it is important to avoid overventilation that can induce central apneas when using spontaneous breathing modes. Noninvasive ventilation in the acute setting seems to be associated with the same sleep abnormalities as invasive ventilation. Long-term noninvasive positive pressure ventilation assists ventilation nocturnally and improves for patients with chronic respiratory failure caused by restrictive thoracic disorders.

Effect of Extracorporeal Membrane Oxygenation Use on Sedative Requirements in Patients with Severe Acute Respiratory Distress Syndrome

To compare sedative dose requirements during the 6‐hour period when they are greatest in patients with severe acute respiratory distress syndrome (ARDS), as well as the time from severe ARDS onset to reach this maximum sedation exposure, between patients with severe ARDS who were managed either with or without extracorporeal membrane oxygenation (ECMO). Also, to explore factors other than ECMO use that may influence sedation requirements during this period of maximum sedation.

Severe Thrombocytopenia in Adults with Severe Acute Respiratory Distress Syndrome: Impact of Extracorporeal Membrane Oxygenation Use.

Extracorporeal membrane oxygenation (ECMO) use is perceived to cause thrombocytopenia (T), but the role of non-ECMO factors in the development of T remains unclear. We sought to evaluate the incidence and factors associated with severe T (platelet count ⩽ 50,000/&mgr;l) in adults with severe acute respiratory distress syndrome (ARDS) managed with or without ECMO. The ECMO (n = 32) versus the non-ECMO (n = 53) groups had a similar baseline platelet count (214,000 vs. 179,000/&mgr;l), Acute Physiology and Chronic Health Evaluation (APACHE) II score (p = 0.13), unfractionated heparin (UFH) exposure (p = 0.62), and severe T incidence (25 vs. 19%, p = 0.5). Although the APACHE II score (p = 0.01), presence of liver failure (p = 0.08), and platelet transfusion (p = 0.0009) were different between the severe T (18/85 [21%]) and non-severe T groups (67/85 [79%]), the incidence of septic shock (p = 0.64), heparin infusion use (p = 0.41), exposure to non-heparin T-causing medications (p = 0.77) and ECMO use (p = 0.5) were not. An adjusted multivariate linear regression model revealed that only the APACHE II score was independently associated with the development of severe T (p = 0.01) but use of ECMO was not (p = 0.32) ECMO use may not affect the incidence of severe T among adults with severe ARDS. Larger studies that are prospective in nature are required to confirm this finding.

Noninvasive Ventilation for Acute Hypoxemic Respiratory Failure/ARDS – is There a Role?

Noninvasive ventilation (NIV) has assumed an important role in the management of acute respiratory failure (ARF) over the past 15 to 20 years. Use of NIV increased substantially during the first decade of the 2000s (1) and it accounts now for approximately 40% of total ventilator starts for ARF and up to 80% of starts in patients with ARF due to exacerbations of COPD or acute cardiogenic pulmonary edema (ACPE) (2). However, the application of NIV in patients with so called de novo acute hypoxemic respiratory failure related to pneumonia or acute respiratory distress syndrome (ARDS) has long been known to be more challenging than in more favorable diagnoses like COPD or ACPE, with NIV failure rates for pneumonia/ARDS exceeding 60% in some studies (3). One epidemiologic study showed that these patients were 3.75 times more likely to fail on NIV than patients with other forms of acute hypoxemic respiratory failure such as chest wall trauma or ACPE (4).

A survey of critical care nurses’ practices and perceptions surrounding early intravenous antibiotic initiation during septic shock

BACKGROUND Delays in antibiotic administration after severe sepsis recognition increases mortality. While physician and pharmacy-related barriers to early antibiotic initiation have been well evaluated, those factors that affect the speed by which critical care nurses working in either the emergency department or the intensive care unit setting initiate antibiotic therapy remains poorly characterized. AIM To evaluate the knowledge, practices and perceptions of critical care nurses regarding antibiotic initiation in patients with newly recognised septic shock. METHODS A validated survey was distributed to 122 critical care nurses at one 320-bed academic institution with a sepsis protocol advocating intravenous(IV) antibiotic initiation within 1hour of shock recognition. RESULTS Among 100 (82%) critical care nurses responding, nearly all (98%) knew of the existence of the sepsis protocol. However, many critical care nurses stated they would optimise blood pressure [with either fluid (38%) or both fluid and a vasopressor (23%)] before antibiotic initiation. Communicated barriers to rapid antibiotic initiation included: excessive patient workload (74%), lack of awareness IV antibiotic(s) ordered (57%) or delivered (69%), need for administration of multiple non-antibiotic IV medications (54%) and no IV access (51%). CONCLUSIONS Multiple nurse-related factors influence IV antibiotic(s) initiation speed and should be incorporated into sepsis quality improvement efforts.