Jean Mantz

Current practices in sedation and analgesia for mechanically ventilated critically ill patients : A prospective multicenter patient-based study

Background:The authors conducted a patient-based survey of practices to fully describe the assessment and the management of pain and sedation of a large cohort of mechanically ventilated patients during their first week of intensive care unit (ICU) stay. Methods:A total of 1,381 adult patients were included in a prospective, observational study in 44 ICUs in France. Pain and sedation assessment, analgesic and sedative use, and analgesic management during procedural pain were collected on days 2, 4, and 6 of the ICU stay. Results:The observed rates of assessment on day 2 for sedation (43%) and analgesia (42%) were significantly smaller than that of use of sedatives (72%) and opioids (90%), also noted on days 4 and 6. The use of protocols/guidelines for sedation/analgesia in the ICU reduced the proportion of patients who were treated, although not evaluated. A large proportion of assessed patients were in a deep state of sedation (40–50%). Minor changes in the dosages of the main prescribed agents for sedation (midazolam, propofol) and analgesia (sufentanil, fentanyl, morphine, remifentanil) were found across 6 days of the patient’s ICU stay. Procedural pain was specifically managed for less than 25% of patients; during those procedures, the proportion of patients with pain significantly increased from the baseline pain evaluation. Conclusions:Excessively deep states of sedation and a lack of analgesia during painful procedures must be prevented. To facilitate systematic pain and sedation assessment and to adjust daily drug dosages accordingly, it seems crucial to promote educational programs and elaboration of protocols/guidelines in the ICU.

Pain assessment is associated with decreased duration of mechanical ventilation in the intensive care unit: A post hoc analysis of the dolorea study

Background:Critically ill patients frequently experience pain, but assessment rates remain below 40% in mechanically ventilated patients. Whether pain assessment affects patient outcomes is largely unknown. Methods:As part of a prospective cohort study of mechanically ventilated patients who received analgesia on day 2 of their stay in the intensive care unit (ICU), the investigators performed propensity-adjusted score analysis to compare the duration of ventilator support and duration of ICU stay between 513 patients who were assessed for pain and 631 patients who were not assessed for pain. Results:Patients assessed for pain on day 2 were more likely to receive sedation level assessment, nonopioids, and dedicated analgesia during painful procedures than patients whose pain was not assessed. They also received fewer hypnotics and lower daily doses of midazolam. Patients with pain assessment had a shorter duration of mechanical ventilation (8 vs. 11 days; P < 0.01) and a reduced duration of stay in the ICU (13 vs. 18 days; P < 0.01). In propensity-adjusted score analysis, pain assessment was associated with increased odds of weaning from the ventilator (odds ratio, 1.40; 95% confidence interval, 1.00–1.98) and of discharge from the ICU (odds ratio, 1.43; 95% confidence interval, 1.02–2.00). Conclusions:Pain assessment in mechanically ventilated patients is independently associated with a reduction in the duration of ventilator support and of duration of ICU stay. This might be related to higher concomitant rates of sedation assessments and a restricted use of hypnotic drugs when pain is assessed.

Can yeast isolation in peritoneal fluid be predicted in intensive care unit patients with peritonitis

ObjectiveTo generate and validate a predictive score of yeast isolation based on independent risk factors of yeast isolation in intensive care unit patients with peritonitis. DesignRetrospective cohort study to determine independent risk factors of yeast isolation, generation of the score, and validation in a prospective cohort of patients with peritonitis. SettingTertiary-care, university-affiliated hospital. PatientsTwo hundred twenty-one patients with peritonitis hospitalized in a surgical intensive care unit between 1994 and 1999 for the retrospective cohort and 57 patients in the prospective cohort (2000). Measurements and Main ResultsFour independent risk factors of yeast isolation in peritoneal fluid (similar odds ratio) were found in the retrospective cohort: female gender, upper gastrointestinal tract origin of peritonitis, intraoperative cardiovascular failure, and previous antimicrobial therapy at least 48 hrs before the onset of peritonitis. A score based on the number of risk factors was constructed (grade A = zero or one risk factor, grade B = at least two risk factors, grade C = at least three risk factors, and grade D = four risk factors), and validated in the prospective cohort. For a grade C score, sensitivity was 84%, specificity was 50%, positive and negative predictive values were 67% and 72%, respectively, and overall accuracy was 71%. ConclusionsFour independent risk factors of yeast isolation in the peritoneal fluid were identified in critically ill surgical patients with peritonitis. The presence of at least three of these factors (grade C score) was associated with a high rate of yeast detection. This approach could be helpful to initiate early antifungal therapy in this patient population.

Postreperfusion syndrome during liver transplantation for cirrhosis: Outcome and predictors

During orthotopic liver transplantation (OLT), a marked decrease in blood pressure following unclamping of the portal vein and liver reperfusion is frequently observed and is termed postreperfusion syndrome (PRS). The predictive factors and clinical consequences of PRS are not fully understood. The goal of this study was to identify predictors of PRS and morbidity/mortality associated with its occurrence during OLT in patients with cirrhosis. During a 3‐year period, all consecutive OLT procedures performed in patients with cirrhosis were studied. Exclusion criteria were OLT for acute liver failure, early retransplantation, combined liver/kidney transplantation, and living‐donor related transplantation. PRS was defined as a decrease in the mean arterial pressure of more than 30% of the value observed in the anhepatic stage, for more than 1 minute during the first 5 minutes after reperfusion of the graft. Transplantation was performed with preservation of the inferior vena cava with or without temporary portocaval shunt. Associations between PRS and donor and recipient demographic data, recipient operative and postoperative outcomes were tested with bivariate statistics. Independent predictors of PRS were determined in multivariable logistic regression analysis. Of the 75 patients included in the study, 20 patients (25%) developed PRS. In a multivariable analysis, absence of a portocaval shunt [odds ratio (95% confidence interval) = 4.42 (1.18‐17.6)] and duration of cold ischemia [odds ratio (95% confidence interval) = 1.34 (1.07‐1.72)] were independent predictors of PRS. Patients who experienced PRS displayed more postoperative renal failure and lower early (<15 days after OLT) survival (80% versus 96%; P = 0.04). In conclusion, the absence of portocaval shunt and the duration of cold ischemia were independent predictors of intraoperative PRS. PRS was associated with significant adverse postoperative outcome. These results provide realistic clinical targets to improve patient outcome after OLT for cirrhosis. Liver Transpl 15:522–529, 2009.

Prospective Validation of the Fifty-Fifty Criteria as an Early and Accurate Predictor of Death After Liver Resection in Intensive Care Unit Patients

Background:Postoperative liver failure after hepatectomy has been identified by the association of prothrombin time <50% and serum bilirubin >50 &mgr;mol/L (the “50–50” criteria). Whether these criteria are of prognostic value in a prospective study remains unknown. Objective:To determine prospectively the prognostic value of the 50–50 criteria on day 3 and day 5 in intensive care unit (ICU) patients after hepatectomy. Methods:From January 2005 to February 2007, among 436 elective liver resections, 99 (23%) consecutive patients aged 58 ± 17 years were admitted postoperatively in ICU with a mean SAPSII 25 ± 10. Malignant disease was present in 87 and major resections (≤3 segments) were performed in 79 (80%) cases. The underlying liver parenchyma was abnormal in 59 (59%) cases including cirrhosis, fibrosis, or steatosis >30% in 19, 23, and 17 patients, respectively. Results:The 50–50 criteria were present on day 3 in 10 patients and on day 5 in 13. Ten patients (10, 6%) died in ICU. Survivors with these criteria were characterized by early aggressive support including reoperation and/or liver assist system. Nonsurvivors were more often cirrhotic, had significantly higher SAPS II and more frequently postoperative prolonged mechanical ventilation. The 50–50 criteria on days 3 and 5 were predictors of death on multivariate analysis [OR (95% CI): 12.7 (2.3–71.4), OR (95% CI): 29.4 (4.9–167), respectively]. Conclusions:After hepatic resection, results of this prospective study validate the 50–50 criteria as a predictive factor of mortality in ICU on both days 3 and 5. These criteria allow an early diagnosis of postoperative liver failure, which may contribute to reduce mortality in ICU patients after hepatectomy.

Predictive factors of early postoperative urinary retention in the postanesthesia care unit

Urinary retention is a common postoperative complication associated with bladder overdistension and the risk of permanent detrusor damage. The goal of this study was to determine predictive factors of early postoperative urinary retention in the postanesthesia care unit (PACU). We prospectively collected, in 313 adult patients, variables including age, gender, previous history of urinary tract symptoms, type of surgery and anesthesia, intraoperative administration of anticholinergics, amount of intraoperative fluids, IV morphine titration, and bladder volume on entry to the PACU. For each patient, bladder volume was measured by ultrasound on entry and before discharge from the PACU. Urinary retention was defined as a bladder volume larger than 600 mL with an inability to void within 30 min. Predictive factors were identified by multivariate analysis. The incidence of urinary retention in the PACU was 16%. In the multivariate analysis only the amount of intraoperative fluids (≥750 mL; P = 0.02; odds ratio = 2.3), age (≥50 yr; P = 0.008; odds ratio = 2.4), and bladder volume on entry to PACU (≥270 mL; P = 0.0001; odds ratio = 4.8) were found to independently increase the risk of urinary retention. Considering the clinical impact of undiagnosed postoperative urinary retention, these results suggest systematic evaluation of bladder volume with a portable ultrasound device in the PACU, especially in patients with risk factors.

Effects of alpha(2)-adrenoceptor agonists on perinatal excitotoxic brain injury: comparison of clonidine and dexmedetomidine.

Background A growing number of children have severe neurologic impairment related to very premature birth. Experimental data suggest that overstimulation of cerebral N-methyl-d-aspartate (NMDA) receptors caused by excessive glutamate release may be involved in the genesis of perinatal hypoxic–ischemic brain injury. &agr;2-Adrenoceptor agonists are protective in models of brain ischemia in adults. The authors sought to determine whether they prevent perinatal excitotoxic neuronal damage. Methods Five-day-old mice were allocated at random to clonidine (4–400 &mgr;g/kg), dexmedetomidine (1–30 &mgr;g/kg), or saline injected intraperitoneally before an intracerebral stereotactic injection of the NMDA receptor agonist ibotenate; cortical and white matter lesions were quantified 5 days later by histopathologic examination. Cortical neuron cultures exposed to 300 &mgr;m NMDA were used to evaluate the effects of clonidine or dexmedetomidine on neuronal death assessed by counting the number of pycnotic nuclei after fluorescent chromatin staining. Results In vivo, both clonidine and dexmedetomidine induced significant concentration-dependent reductions in the size of ibotenate-induced lesions in the cortex and white matter. In vitro, the number of neurons damaged by NMDA exposure was significantly decreased by both dexmedetomidine (−28 ± 12% at 10 &mgr;m;P < 0.01) and clonidine (−37 ± 19% at 100 &mgr;m;P < 0.01) as compared with controls. In both models, the selective &agr;2-adrenoceptor antagonist yohimbine abolished the neuroprotective effect of clonidine and dexmedetomidine. Conclusions Clonidine and dexmedetomidine are potent neuroprotectors that act by stimulating the &agr;2 adrenoceptors. These results obtained in a murine model of perinatal excitotoxic injury may be relevant to some forms of neonatal brain damage in humans.

Dexmedetomidine: new insights.

Dexmedetomidine is a potent alpha-2-adrenergic agonist, more selective than clonidine, with widespread actions on the mammalian brain that include sedation, anaesthetic-sparing, analgesia and sympatholytic properties. A large body of recent work supports its favourable profile in improving outcome and long-term brain function in the critically ill. The source of these benefits may lie in the neuroprotective properties that are seen in experimental models and in the clinical setting, in which it can attenuate delirium, preserve sleep architecture, preserve ventilatory drive and decrease sympathetic tone and inflammatory response. Dexmedetomidine may also be a valuable adjuvant when regional anaesthesia is used. Future research should aim at establishing the risk/benefit ratio when used at the bedside.

Effects of General Anesthetics on Intercellular Communications Mediated by Gap Junctions between Astrocytes in Primary Culture

Background:Astrocytes represent a major nonneuronal cell population in the central nervous system (CNS) and are actively involved in several brain functions. These cells are coupled by gap junctions (GJ) into a syncytial-like network resulting in cellular communication through ionic and metabolic exchange between adjacent astrocytes. Whether anesthetics affect astrocyte function is not known. In the present study, the effects of general anesthetics on GJ permeability were investigated in primary cultures of mouse striatal astrocytes. Methods:Junctional permeability was determined by using the fluorescent probe Lucifer yellow and the scrape loading/dye transfer technique. Confluent cells were preincubated 5 min with various concentrations of anesthetic agents and GJ permeability was estimated by measuring the area occupied by the dye from digitalized images taken 8 min after cell loading. Results:Of the intravenous anesthetics tested, only propofol (P: 10-4M, P > 0.01 and 10>-5M, P > 0.05) and etomidate (ET: 10−4M, P > 0.05, but not 10−5) induced a significant reduction of GJ permeability. In contrast, diazepam (10−5M), morphine (10−4M), ketamine (10−4M), thiopental (10−4M), and clonidine (10−7M) did not affect junctional permeability. In addition, the halogenated anesthetics halothane, enflurane, and isoflurane induced a dose-dependent closure of GJ. For halothane, enflurane, and isoflurane, the maximum effect was achieved with a 10−4M, 1.6 X 10−3M, and 10-3M anesthetic concentration, respectively. Removal of volatile anesthetics resulted in the restoration of the control fluorescence area between 15 and 45 min. The time course of recovery of GJ permeability was examined more precisely for shorter periods of halothane administration (5 min, 1 mM). Under these conditions, the rate of dye spread returned to control values following anesthetic washout, while, during the same period of time, complete uncoupling of GJ was still observed in the presence of a 1 mM halothane concentration. Conclusions:These results indicate that general anesthetics differentially affect GJ permeability in cultured astrocytes. This uncoupling effect (closure of gap junctions) may contribute to the mechanisms of action of some anesthetic agents (primarily volatile anesthetics) at the level of the CNS by altering astrocyte communication.

Misrepresentation of randomized controlled trials in press releases and news coverage: a cohort study.

A study conducted by Amélie Yavchitz and colleagues examines the factors associated with “spin” (specific reporting strategies, intentional or unintentional, that emphasize the beneficial effect of treatments) in press releases of clinical trials.