Paul M. Szumita

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.

Barriers to Glucose Control in the Intensive Care Unit

Despite published evidence supporting glycemic control in critically ill patients, achieving euglycemia remains a problem in the intensive care units (ICUs) of many institutions. Clinicians seeking to implement the findings of published evidence in their practice face many potential barriers that make euglycemia difficult to achieve in patients in the ICU. Developing a comprehensive understanding of the many barriers to ICU glucose control can aide clinicians in attempting to change practice and improve patient outcomes. Barriers to ICU glucose control include the role of different health professionals in glucose management, communication among health care professionals, guidelines, protocols, ICU culture, fear of hypoglycemia, glucose monitoring, education, systems analysis, health care resources, nutritional needs, and drug utilization. By ensuring compliance, changing ICU culture, developing guidelines and protocols, and incorporating a multidisciplinary approach, clinicians can achieve glycemic control in the critically ill population and improve patient outcomes.

Inhaled epoprostenol vs inhaled nitric oxide for refractory hypoxemia in critically ill patients

PURPOSE The purpose of this is to compare efficacy, safety, and cost outcomes in patients who have received either inhaled epoprostenol (iEPO) or inhaled nitric oxide (iNO) for hypoxic respiratory failure. MATERIALS AND METHODS This is a retrospective, single-center analysis of adult, mechanically ventilated patients receiving iNO or iEPO for improvement in oxygenation. RESULTS We evaluated 105 mechanically ventilated patients who received iEPO (52 patients) or iNO (53 patients) between January 2009 and October 2010. Most patients received therapy for acute respiratory distress syndrome (iNO 58.5% vs iEPO 61.5%; P=.84). There was no difference in the change in the partial pressure of arterial O2/fraction of inspired O2 ratio after 1 hour of therapy (20.58±91.54 vs 33.04±36.19 [P=.36]) in the iNO and iEPO groups, respectively. No difference was observed in duration of therapy (P=.63), mechanical ventilation (P=.07), intensive care unit (P=.67), and hospital lengths of stay (P=.26) comparing the iNO and iEPO groups. No adverse events were attributed to either therapy. Inhaled nitric oxide was 4.5 to 17 times more expensive than iEPO depending on contract pricing. CONCLUSIONS We found no difference in efficacy and safety outcomes when comparing iNO and iEPO in hypoxic, critically ill patients. Inhaled epoprostenol is associated with less drug expenditure than iNO.

Evaluation of Compliance with a Paper-based, Multiplication-factor, Intravenous Insulin Protocol

Background: Hyperglycemia is common in critically ill patients and is an independent risk factor for in-hospital morbidity and mortality. Objective: To assess compliance with a paper-based, multiplication-factor, intravenous insulin protocol. Methods: A retrospective chart review was conducted in a 720-bed urban, academic medical center in Boston, Massachusetts. During a 1-month period, compliance with and the consequent safety and efficacy of the Brigham and Womens Hospital paper-based, multiplication-factor, intravenous insulin protocol was evaluated. Results: The primary endpoint of protocol compliance, defined as correct adjustment to insulin infusion rate and correct timing of bedside blood glucose concentration (BBGC) checks ±10 minutes of prespecified BBGC check according to the Brigham and Womens Hospital Intravenous Insulin Protocol (BHIP), was 47.2%. Seventy-two patients met inclusion criteria. Appropriate adjustment of infusion rates occurred 68.2% (1206/1768) of the time. Compliance with the timing of BBGC checks was found to be the majority of protocol violations. BBGCs were monitored ±5 minutes of indicated time per the protocol 26.2% (463/1768) of the time. Blood glucose concentration checks within extended timing of ±10 minutes of indicated time per the protocol occurred 793 (44.8%) times. Blood glucose concentration monitoring took place greater than 20 minutes past indicated time 450 (25.5%) times. In 1768 measurements, blood glucose concentrations between 40 and 60 mg/dL occurred 23 (1.3%) times in 12 (16.7%) patients. Blood glucose concentrations 40 mg/dL or less were detected 3 (0.17%) times in 2 (2.7%) patients. None of these hypoglycemic events led to documented complications. Conclusions: Overall, a rather low level of compliance with a paper-based, multiplication-factor, intravenous insulin protocol was observed, which warrants further investigation. Compliance rates in this evaluation were found to be similar to the rates observed in previously evaluated fixed-dose intravenous insulin protocols. Protocol noncompliance may be associated with hypo- and hyperglycemia.

Evaluation of dexmedetomidine versus propofol-based sedation therapy in mechanically ventilated cardiac surgery patients at a tertiary academic medical center.

Management of pain and sedation therapy is a vital component of optimizing patient outcomes; however, the ideal pharmacotherapy regimen has not been identified in the postoperative cardiac surgery population. We sought to evaluate efficacy and safety outcomes between postoperative mechanically ventilated cardiac surgery patients receiving dexmedetomidine versus propofol therapy upon arrival to the intensive care unit (ICU). We conducted a single center, descriptive study of clinical practice at a 20-bed cardiac surgery ICU in a tertiary academic medical center. Adult mechanically ventilated postcardiac surgery patients who received either dexmedetomidine or propofol for sedation therapy upon admission to the ICU between October 20, 2006 and December 15, 2006 were evaluated. A pharmacy database was used to identify patients receiving dexmedetomidine or propofol therapy for perioperative sedation during cardiac surgery. Patients were matched according to surgical procedure type. Fifty-six patients who received either dexmedetomidine (n = 28) or propofol (n = 28) were included in the analysis. No differences in the ICU length of stay (58.67 ± 32.61 vs. 61 ± 33.1 hours; P = 0.79) and duration of mechanical ventilation (16.21 ± 6.05 vs. 13.97 ± 4.62 hours; P = 0.13) were seen between the propofol and dexmedetomidine groups, respectively. Hypotension (17 [61%] vs. 9 [32%]; P = 0.04), morphine use (11 [39.3%] vs. 1 [3.6%]; P = 0.002), and nonsteroidal anti-inflammatory use (7 [25%] vs. 1 [3.6%]; P = 0.05) occurred more during dexmedetomidine therapy versus propofol. Dexmedetomidine therapy resulted in a higher incidence of hypotension and analgesic consumption compared with propofol-based sedation therapy. Further evaluation is needed to assess differences in clinical outcomes of propofol and dexmedetomidine-based therapy in mechanically ventilated cardiac surgery patients.

Azacitidine-induced interstitial and alveolar fibrosis in a patient with myelodysplastic syndrome.

A 71‐year‐old Caucasian man diagnosed with myelodysplastic syndrome developed interstitial and alveolar fibrosis after receiving a 7‐day course of azacitidine therapy. The patients pulmonary function began to deteriorate immediately after the administration of his chemotherapy regimen. Other potential causes of pulmonary toxicity were ruled out such as viral, fungal, and bacterial pathogens, as well as other concomitant drugs. To our knowledge, this is the first case report documenting biopsy‐proven interstitial and alveolar fibrosis associated with azacitidine. The frequency of this adverse drug reaction is unknown but may become more evident with increasing exposure of the population to azacitidine.

Extensive Prolongation of aPTT with Argatroban in an Elderly Patient with Improving Renal Function, Normal Hepatic Enzymes, and Metastatic Lung Cancer

OBJECTIVE: To report a case of an elderly male with improving renal function and normal hepatic function who sustained an elevated activated partial thromboplastin time (aPTT) after an infusion of argatroban was discontinued. CASE SUMMARY: A 77-year-old white male with a history of heparin-induced thrombocytopenia (HIT) and metastatic lung disease was started on argatroban for treatment of a right upper-extremity deep vein thrombosis (DVT). The infusion was initiated at 2.0 μg/kg/min and was titrated to a goal aPTT of 60–80 seconds. Argatroban was discontinued due to an aPTT elevated to >100 seconds; the aPTT remained elevated for 130 hours after discontinuation of the infusion. DISCUSSION: Argatroban dose reductions in patients with impaired liver and renal function test values have been reported. Elderly subjects may have a prolonged clearance compared with young healthy subjects, although the duration of effect has not been established. As of April 18, 2005, the effect of liver metastasis on argatroban pharmacokinetics in the setting of normal liver function enzyme levels has not been reported. An objective causality assessment using the Naranjo probability scale showed that the prolonged aPTT was probably attributable to argatroban. CONCLUSIONS: Clinicians should exercise caution when initiating argatroban at a dose of 2.0 μg/kg/min in elderly patients with underlying comorbidities, such as metastatic disease and renal impairment, since this may lead to excessive and prolonged anticoagulation and increased risk of bleeding.

Implementation of a Hospital-wide Protocol for Induced Hypothermia Following Successfully Resuscitated Cardiac Arrest.

Permanent neurologic impairment following cardiac arrest is often severely debilitating, even after successful resuscitation. Therapeutic hypothermia decreases anoxic brain injury and subsequent cognitive deficits. Current practice guidelines recommend therapeutic hypothermia in comatose survivors of cardiac arrest. To address the multifacets of therapeutic hypothermia, we assembled a multidisciplinary task force including members from various specialties to create an evidence-based guideline with transparency across disciplines and consistency of care. We describe our institutional guidelines for the initiation and management of induced hypothermia in patients successfully resuscitated from a cardiac arrest.

Early vasopressin reduces incidence of new onset arrhythmias

PURPOSE The objective of this study was to determine the effect of early vs late vasopressin therapy on catecholamine dose and duration. MATERIALS AND METHODS We conducted a single-center, retrospective chart review of adult patients admitted to the medical intensive care unit between January 2010 and December 2011 with septic shock requiring catecholamine and vasopressin therapy. Patients were included in the early group if vasopressin was initiated within 6 hours and the late group if vasopressin was initiated between 6 and 48 hours of catecholamine(s). RESULTS Duration of catecholamine and vasopressin therapy was similar between the 35 patients in the early group and the 36 in the late group. Vasopressin therapy was associated with a decrease in catecholamine requirements in both groups. Early vasopressin was associated with fewer new onset arrhythmias (37.1% vs 62.9%, P<.001). There was no difference in mortality, hospital, or intensive care unit length of stay between the early and late group vasopressin groups (88.6% vs 88.9%, P=1; 14 vs 10 days, P=.48; 9 vs 7 days, P=.71, respectively). CONCLUSIONS Early initiation of vasopressin therapy in adult critically ill patients with septic shock was associated with no difference in total catecholamine requirements but decreased incidence of new onset arrhythmias.

Pathophysiology, assessment, and management of pain in critically ill adults.

PURPOSE The pathophysiology of pain in critically ill patients, the role of pain assessment in optimal pain management, and pharmacologic and nonpharmacologic strategies for pain prevention and treatment are reviewed. SUMMARY There are many short- and long-term consequences of inadequately treated pain, including hyperglycemia, insulin resistance, an increased risk of infection, decreased patient comfort and satisfaction, and the development of chronic pain. Clinicians should have an understanding of the basic physiology of pain and the patient populations that are affected. Pain should be assessed using validated pain scales that are appropriate for the patients communication status. Opioids are the cornerstone of pain treatment. The use of opioids, administered via bolus dosing or continuous infusion, should be guided by patient-specific goals of care in order to avoid adverse events. A multimodal approach to pain management, including the use of regional analgesia, may improve patient outcomes and decrease opioid-related adverse events, though there are limited relevant data in adult critically ill patient populations. Nonpharmacologic strategies have been shown to be effective adjuncts to pharmacologic regimens that can improve patient-reported pain intensity and reduce analgesic requirements. Analgesic regimens need to take into account patient-specific factors and be closely monitored for safety and efficacy. CONCLUSION Acute pain management in the critically ill is a largely underassessed and undertreated area of critical care. Opioids are the cornerstone of treatment, though a multimodal approach may improve patient outcomes and decrease opioid-related adverse events.