Jacques-André Romand

Randomized trial of light versus deep sedation on mental health after critical illness

Objectives:To investigate if light sedation favorably affects subsequent patient mental health compared with deep sedation. Symptoms of posttraumatic stress disorder are common in patients after they have undergone prolonged mechanical ventilation and are associated with sedation depth. Design:Randomized, open-label, controlled trial. Setting:Single tertiary care center. Patients:Adult patients requiring mechanical ventilation. Interventions:Patients were randomized to receive either light (patient awake and cooperative) or deep sedation (patient asleep, awakening upon physical stimulation). Measurements and Main Results:Self-reported measures of posttraumatic stress disorder, anxiety, and depression were collected at intensive care unit discharge and 4 wks later. The primary outcomes were symptoms of posttraumatic stress disorder, anxiety, and depression 4 wks after intensive care unit discharge. A total of 137 patients were assigned to either the light (n = 69) or the deep sedation (n = 68) group. Seven patients withdrew consent and one patient was randomized in error, leaving 129 patients (n = 65 in light sedation and n = 64 in deep sedation) available for analysis. At the 4-wk follow-up, patients in the deep sedation group tended to have more posttraumatic stress disorder symptoms (p = .07); the deep sedation group had more trouble remembering the event (37% vs. 14%; p = .02) and more disturbing memories of the intensive care unit (18% vs. 4%; p = .05). Patients in the light sedation group had an average one day less being ventilated and 1.5 fewer days in the intensive care unit. There were no differences between the two groups in the occurrence of anxiety and depression, and also no difference in mortality or in the incidence of adverse events. Conclusions:These data suggest that a strategy of light sedation affords benefits with regard to reduction of intensive care unit stay and duration of ventilation without negatively affecting subsequent patient mental health or patient safety.

Review of medical prevention of vasospasm after aneurysmal subarachnoid hemorrhage: a problem of neurointensive care.

CEREBRAL VASOSPASM REMAINS a devastating medical complication of aneurysmal subarachnoid hemorrhage (SAH). It is associated with high morbidity and mortality rates, even after the aneurysm has been secured surgically or radiologically. A great deal of experimental and clinical research has been conducted in an effort to find ways to prevent this complication. The literature includes extensive coverage of in vivo animal model studies of SAH and vasospasm. These experimental studies have contributed to tremendous advances in the understanding of the mechanisms leading to cerebral vasospasm. Most of the experimental settings, however, have demonstrated varying levels of ability to predict accurately what occurs in human SAH. Therefore, although animal models have been developed to test new therapies, most of the treatment effects have been shown to be less compelling when trials have been conducted in clinical settings. The interpretation of current literature is complicated further by the imprecise estimation of the incidence of cerebral vasospasm, which is due to various degrees of clinical expression, ranging from the absence of symptoms in the presence of increased blood flow velocities at transcranial Doppler or vessel diameter reduction at angiography to neurological manifestations of severe ischemic deficits. In addition, a change over time in the incidence pattern of human SAH and vasospasm, possibly related to improved surgical techniques and overall patient management, may have occurred. This topic review collects the relevant literature on clinical trials investigating prophylactic therapies for cerebral vasospasm in patients with aneurysmal SAH and emphasizes the need for large clinical trials to confirm the results derived from clinical experience. In addition, it points out some experimental therapies that may hold promise in future clinical trials to prevent the occurrence of vasospasm.

Cefepime versus Imipenem-Cilastatin for Treatment of Nosocomial Pneumonia in Intensive Care Unit Patients: a Multicenter, Evaluator-Blind, Prospective, Randomized Study

ABSTRACT In a randomized, evaluator-blind, multicenter trial, we compared cefepime (2 g three times a day) with imipenem-cilastatin (500 mg four times a day) for the treatment of nosocomial pneumonia in 281 intensive care unit patients from 13 centers in six European countries. Of 209 patients eligible for per-protocol analysis of efficacy, favorable clinical responses were achieved in 76 of 108 (70%) patients treated with cefepime and 75 of 101 (74%) patients treated with imipenem-cilastatin. The 95% confidence interval (CI) for the difference between these response rates (−16 to 8%) failed to exclude the predefined lower limit for noninferiority of −15%. In addition, therapy of pneumonia caused by an organism producing an extended-spectrum β-lactamase (ESBL) failed in 4 of 13 patients in the cefepime group but in none of 10 patients in the imipenem group. However, the clinical efficacies of both treatments appeared to be similar in a secondary intent-to-treat analysis (95% CI for difference, −9 to 14%) and a multivariate analysis (95% CI for odds ratio, 0.47 to 1.75). Furthermore, the all-cause 30-day mortality rates were 28 of 108 (26%) patients in the cefepime group and 19 of 101 (19%) patients in the imipenem group (P = 0.25). Rates of documented or presumed microbiological eradication of the causative organism were similar with cefepime (61%) and imipenem-cilastatin (54%) (95% CI, −23 to 8%). Primary or secondary resistance of Pseudomonas aeruginosa was detected in 19% of the patients treated with cefepime and 44% of the patients treated with imipenem-cilastatin (P = 0.05). Adverse events were reported in 71 of 138 (51%) and 62 of 141 (44%) patients eligible for safety analysis in the cefepime and imipenem groups, respectively (P = 0.23). Although the primary end point for this study does not exclude the possibility that cefepime was inferior to imipenem, some secondary analyses showed that the two regimens had comparable clinical and microbiological efficacies. Cefepime appeared to be less active against organisms producing an ESBL, but primary and secondary resistance to imipenem was more common for P. aeruginosa. Selection of a single agent for therapy of nosocomial pneumonia should be guided by local resistance patterns.

Transcutaneous PCO2 monitoring in critically ill adults: clinical evaluation of a new sensor.

Objective:In critically ill patients, arterial blood gas analysis is the gold standard for evaluating systemic oxygenation and carbon dioxide partial pressure. A new miniaturized carbon dioxide tension Pco2-Spo2 single sensor (TOSCA, Linde Medical Sensors AG, Basel, Switzerland) continuously and noninvasively (transcutaneously) monitors both Paco2 and oxygen saturation by pulse oximetry (Spo2). The present study was designed to investigate the usability and the accuracy of this device in critically ill patients. Design:Prospective clinical investigation. Setting:A 20-bed, university-affiliated, surgical intensive care unit. Patients:Patients admitted after major surgery, multiple trauma, or septic shock equipped with an arterial catheter. Interventions:The heated (42°C) sensor was fixed at the earlobe using an attachment clip. Transcutaneous Pco2 (TcPco2) measurements were correlated with Paco2 values (measured using a blood gas analyzer). In addition, the differences between Paco2 and TcPco2 values were evaluated using the method of Bland-Altman. Measurements and Main Results:We studied 55 patients, aged 18–80 (mean 57 ± 15) yrs. A total of 417 paired measurements were compared. Correlation between TcPco2 and Paco2 was r = .86 (p < .01) in the Paco2 range of 24–101 mm Hg. Mean bias (±sd) between the two methods of measurement (Bland-Altman analysis) was 1.2 ± 6.0 mm Hg with TcPco2 slightly overestimating arterial carbon dioxide tension. Nineteen percent of the measured values were outside of the acceptable clinical range of agreement of ±7.5 mm Hg. Conclusions:The present study suggests that Paco2 can be acceptably assessed by measuring TcPco2 using the TOSCA Pco2-Spo2 sensor.

Fluid responsiveness in spontaneously breathing patients : A review of indexes used in intensive care

LEARNING OBJECTIVESOn completion of this article, the reader should be able to: Define static and dynamic indexes. List indexes that are valuable to predict fluid responsiveness in spontaneously breathing patients. Use this information in a clinical setting. All authors have disclosed that they have no financial relationships or interests in any commercial companies pertaining to this educational activity. Wolters Kluwer Health has identified and resolved all faculty conflicts of interest regarding this educational activity. Visit the Critical Care Medicine Web site (www.ccmjournal.org) for information on obtaining continuing medical education credit. Objective:In spontaneously breathing patients, indexes predicting hemodynamic response to volume expansion are very much needed. The present review discusses the clinical utility and accuracy of indexes tested as bedside indicators of preload reserve and fluid responsiveness in hypotensive, spontaneously breathing patients. Data Source:We conducted a literature search of the MEDLINE database and the trial register of the Cochrane Group. Study Selection:Identification of reports investigating, prospectively, indexes of fluid responsiveness in spontaneously breathing critically ill patients. All the studies defined the response to fluid therapy after measuring cardiac output and stroke volume using the thermodilution technique. We did not score the methodological quality of the included studies before the data analysis. Data Extraction:A total of eight prospective clinical studies in critically ill patients were included. Only one publication evaluated cardiac output changes induced by fluid replacement in a selected population of spontaneously breathing critically ill patients. Data Synthesis:Based on this review, we can only conclude that static indexes are valuable tools to confirm that the fluid volume infused reaches the cardiac chambers, and therefore these indexes inform about changes in cardiac preload. However, respiratory variation in right atrial pressure, which represents a dynamic measurement, seems to identify hypotension related to a decrease in preload and to distinguish between responders and nonresponders to a fluid challenge. Conclusions:Further studies should address the question of the role of static indexes in predicting cardiac output improvement following fluid infusion in spontaneously breathing patients.

Effect of increasing norepinephrine dosage on regional blood flow in a porcine model of endotoxin shock

ObjectiveTo evaluate the effect of a norepinephrine-induced differential increase in mean arterial pressure on splanchnic and renal perfusion in a porcine model of volume-resuscitated endotoxic shock. DesignProspective, controlled, acute interventional study. SettingAnimal research laboratory. SubjectsFourteen landrace pigs, seven treated with norepinephrine and seven used as endotoxemic controls. InterventionsIn an acute endotoxic shock model, norepinephrine was used to reverse hypotension in seven fluid-resuscitated pigs, anesthetized with &agr;-chloralose and equipped with flow probes around the portal vein and renal artery, renal and jejunal mucosal laser Doppler flowmetry, and jejunal tonometry. Mean arterial pressure was increased by 10 and then 20 mm Hg above the shock level with norepinephrine. Seven shocked, fluid-resuscitated only animals served as the comparison group. Measurements and Main ResultsMeasurements were performed before 2-hr endotoxin infusion and at the end of each increased level of mean arterial pressure. Raising mean arterial pressure with norepinephrine by 10 mm Hg significantly increased cardiac output, systemic oxygen extraction, and portal vein blood flow; stabilized metabolic acidosis; and tended to restore renal and jejunal mucosal flows to preshock levels. Increasing mean arterial pressure by 20 mm Hg further increased cardiac output and oxygen delivery but without improving portal vein, renal artery, and jejunal mucosal blood flows. ConclusionsNorepinephrine, administered to increase mean arterial pressure by 10 mm Hg in an acute model of volume-resuscitated endotoxic shock, improved systemic and regional perfusion. The administration of norepinephrine to increase mean arterial pressure 20 mm Hg above shock did not increase renal and splanchnic blood flows, despite an enhanced cardiac output.

Long-term prognosis after acute kidney injury requiring renal replacement therapy

BACKGROUND Data on the long-term survival and renal function of patients with acute kidney injury (AKI) treated with continuous renal replacement therapy are scarce. METHODS We investigated the 3-year survival and need for chronic dialysis in critically ill patients, who had survived an episode of AKI requiring continuous renal replacement therapy. RESULTS A total of 206 ICU patients with AKI were randomized in a trial comparing haemofiltration versus haemodiafiltration. Of these, 95 (46%) survived at 90 days. Post-discharge information relating to 3-year survival and renal function was successfully obtained in 89 (94%) of the patients. Of the 89 patients studied, chronic kidney disease (CKD) was present in 32 subjects from the onset, and CKD developed de novo in 25 patients following AKI. End-stage renal disease (ESRD) developed in 9 patients (of whom 8 had pre-existing CKD) and 29 patients died. Three-year survival was 67% overall; the mortality at 3 years was 50% for those with pre-existing kidney disease, and 71 and 82% for those with de novo and without CKD, respectively. CONCLUSION After an episode of AKI necessitating a continuous renal replacement therapy, rapid progression to ESKD is commonly observed in patients with pre-existing chronic renal impairment. Medical care with an emphasis on nephroprotection is necessary in these patients.

Cervical Sympathetic Block to Reverse Delayed Ischemic Neurological Deficits After Aneurysmal Subarachnoid Hemorrhage

Background and Purpose— The purpose of the present study was to evaluate the feasibility and safety of a locoregional cervical sympathetic block to improve cerebral perfusion in patients suffering from cerebral vasospasm after aneurysmal subarachnoid hemorrhage. Methods— Nine consecutive patients with symptoms of delayed ischemic deficits, induced by angiographically confirmed cerebral vasospasm, were treated with the injection of locoregional anesthesia to block the ascending cervical sympathetic chain at the level of the superior cervical ganglion. Neurological status was recorded before and after the procedure, and cerebral angiography was performed before and after the procedure. Results— No complications occurred in this short series. The procedure appeared to be simple and safe. Horner’s signs appeared within 12±0.1 minutes and lasted for an average of 6.3±4 hours. In all patients, improved cerebral perfusion was detected at the confirmatory angiography but without change in vessel caliber. One patient died of the complications of the initial hemorrhage, and 2 died of the consequences of the severe vasospasm despite maximal medical treatment. In all the other cases, the neurological status promptly returned to normal within 48 hours after the locoregional treatment. Conclusions— Patients with mild to moderate symptoms seem to benefit greatly from transient ipsilateral cervical sympathetic block. This simple technique may be helpful when used as an adjunct to the standard therapy to improve cerebral perfusion.

Lack of effect of combination antibiotic therapy on mortality in patients with pneumococcal sepsis

In order to determine whether combination antibiotic therapy decreases mortality after severe pneumococcal infection, a retrospective study of a cohort of 1,840 adult patients with severe sepsis or septic shock enrolled in two multicenter clinical trials between 1994 and 1999 was conducted. Among 107 patients with monobacterial pneumococcal sepsis, the case-fatality rate was 20% (five of 25) for patients who received antibiotic monotherapy compared with 19.5% (16 of 82) for patients who received combination therapy (adjusted hazard ratio, 1.1; 95% CI, 0.4–3.1). Similarly, monotherapy did not increase the risk of death (adjusted hazard ratio, 1.0; 95% CI, 0.2–4.8) among bacteremic patients (n=75). However, the latter analysis may have been underpowered (power, 58%) to detect a difference in mortality. Overall, in contrast to recently published reports, these results suggest that combination antibiotic therapy does not decrease mortality after severe pneumococcal sepsis.

A nationwide survey of intensive care unit discharge practices

ObjectiveTo describe intensive care unit (ICU) discharge practices, examine factors associated with physicians’ discharge decisions, and explore ICU and hospital characteristics and clinical determinants associated with the discharge process.DesignSurvey in adult ICUs affiliated with the Swiss Society of Intensive Care Medicine.InterventionsQuestionnaire inquiring about ICU structure and organization mailed to 73 medical directors. Level of monitoring, intravenous medications, and physiological variables were proposed as elements of discharge decision. Five clinical situations were presented with request to assign a discharge disposition.Measurements and resultsFifty-five ICUs participated, representing 75% of adult Swiss ICUs. Responsibility for patient management was assigned in 91% to the ICU team directing patient care. Only 22% of responding centers used written discharge guidelines. One-half of the respondents considered at least 10 of 15 proposed criteria to decide patient discharge. ICUs in central referral hospitals used fewer criteria than community and private hospitals. The availability of intermediate care units was significantly greater in university hospitals. The ICU director’s level of experience was not associated with the number of criteria used. In the five clinical scenarios there was wide variation in discharge decision.ConclusionsOur data indicate that there is marked heterogeneity in ICUs discharge practices, and that discharge decisions may be influenced by institutional factors. University teaching hospitals had more intermediate care facilities available. Written discharge guidelines were not widely used.