Intra-individual variation of the cuff-leak test as a predictor of post-extubation stridor.

BACKGROUND: This was an evaluation of intra-individual variation of the cuff-leak test (ΔCLT) immediately post-intubation and pre-extubation, as a predictor of post-extubation stridor. METHODS: Prospective, clinical investigation in the ICU of a non-university hospital. CLTs were performed immediately after intubation (T0) and before extubation (T1) to evaluate the differences in cuff leak (ΔCLT = CL(T1) - CL(T0)). RESULTS: We included 104 mechanically ventilated subjects in the study over a 12-month period. The incidence of post-extubation stridor was 6.7%. Stridor was more common in females of short stature. ΔCLT was considered as significant when CL(T1) - CL(T0) was negative. The sensitivity and the specificity of the test were 86% and 48%, respectively. When we tested the pre-extubation CLT alone with a threshold of 130 mL as a predictor of post-extubation stridor, the sensitivity and the specificity of the test were 86% and 76%, respectively. CONCLUSIONS: The intra-individual variation of CLT immediately post-intubation and pre-extubation does not improve the accuracy of a standard pre-extubation CLT to predict post-extubation stridor. Moreover, the standard pre-extubation CLT did not appear in our study to be an ideal test to detect post-extubation stridor. Larger studies should be performed before generalizing these preliminary results.

Exogenous natural surfactant for treatment of acute lung injury and the acute respiratory distress syndrome.

RATIONALE: Compositional changes in surfactant and/or decreased surfactant content of the lungs are common features in patients with acute respiratory failure. Instillation of exogenous surfactant into the lungs of neonates with respiratory distress syndrome or pediatric patients with acute respiratory distress syndrome (ARDS) has resulted in improved survival. OBJECTIVES: We conducted this trial to determine whether the instillation of exogenous surfactant would improve the Day 28 outcome of adult patients with acute lung injury (ALI) or ARDS. METHODS: A total of 418 patients with ALI and ARDS were included in an international, multicenter, stratified, randomized, controlled, open, parallel-group study. We randomly assigned 418 patients to receive usual care either with or without instillation of exogenous natural porcine surfactant HL 10 as large boluses. MEASUREMENTS AND MAIN RESULTS: The primary endpoint was death rate before or on Day 28. Secondary endpoints were adverse event and death rate on day 180. The 28-day death rate in the usual care group was 24.5% compared with 28.8% in the HL 10 group. The estimated odds ratio for death at Day 28 in the usual care group versus the HL 10 group was 0.75 (95% CI, 0.48-1.18; P = 0.22). The most common adverse events related to HL 10 administration were temporary hypoxemia defined as oxygen saturation less than 88% (51.9% in HL 10 group vs. 25.2% in usual care) and hypotension defined as mean arterial blood pressure less than 60 mm Hg (34.1% in HL 10 group vs. 17.1% in usual care). CONCLUSIONS: In this study, instillation of a large bolus of exogenous natural porcine surfactant HL 10 into patients with acute lung injury and ARDS did not improve outcome and showed a trend toward increased mortality and adverse effects. Clinical trial registered with www.clinicaltrials.gov (NCT 00742482).

Early tracheotomy versus prolonged endotracheal intubation in unselected severely ill ICU patients.

OBJECTIVE: Although several advantages are attributed to tracheotomy in ICU patients requiring mechanical ventilation (MV), true benefits and the optimal timing of tracheotomy remain controversial. In this study, we compared early tracheotomy (ET) with prolonged intubation (PI) in severely ill patients requiring prolonged MV. DESIGN: Prospective, randomized study. SETTING: Twenty-five medical and surgical ICUs in France. PATIENTS: Patients expected to require MV > 7 days. MEASUREMENTS AND RESULTS: Patients were randomised to either (open or percutaneous) ET within 4 days or PI. The primary end-point was 28-day mortality. Secondary end-points were: the incidence of ICU-acquired pneumonia, number of d1-d28 ventilator-free days, time spent in the ICU, 60-day mortality, number of septic episodes, amount of sedation, comfort and laryngeal and tracheal complications. A sample size of 470 patients was considered necessary to obtain a reduction from 45 to 32% in 28-day mortality. After 30 months, 123 patients had been included (ET = 61, PI = 62) in 25 centres and the study was prematurely closed. All group characteristics were similar upon admission to ICU. No difference was found between the two groups for any of the primary or secondary end-points. Greater comfort was the sole benefit afforded by tracheotomy after subjective self-assessment by patients. CONCLUSIONS: The trial did not demonstrate any major benefit of tracheotomy in a general population of ICU patients, as suggested in a previous meta-analysis, but was underpowered to draw any firm conclusions. The potential advantage of ET may be restricted to selected groups of patients.

A four-step protocol for limitation of treatment in terminal care. An observational study in 475 intensive care unit patients.

OBJECTIVE: To describe a four-step protocol for withholding and withdrawal of life support (WH/WDLS) in intensive care unit (ICU) terminal patients. DESIGN: Observational study. SETTING: A 10-bed ICU of a general hospital. PATIENTS: Eighty-three patients out of 475 consecutive patients admitted over a 1 year period had WH/WDLS. INTERVENTIONS: The healthcare team chose a pattern of treatment limitation on a four-step protocol for every patient every day. There were four alternatives: group 1: no limitation of care; group 2: patient designated do not resuscitate (DNR) and pressors limited to dopamine at a maximum dose of 20 microg/kg per min; others therapies were continued; group 3: active withdrawal of all therapy except comfort care, i.e., the patient continued to receive nursing, sedation/analgesia, hydration and mechanical ventilation with FIO2=0.21 and no positive end-expiratory pressure (PEEP). Sedation was adjusted to Ramsay 3-4. The group 4 was treated the same as group 3 except that minute ventilation was 5 l/min and sedation/analgesia adjusted to Ramsay 6. WH/WDLS was performed only if the full ICU staff and all family members agreed with the procedure. WH/WDLS was documented in the patient's chart. RESULTS: Withholding and withdrawal of life support was performed in 83 patients (17%): 25 patients in group 2 (15 deaths), 36 patients in group 3 (36 deaths) and 22 patients in group 4 (22 deaths). Finally, 73 patients died after WH/WDLS. ICU stay was 10+/-17 days, time from admission to WH/WDLS was 184+407 h and time from WH/WDLS to death was 64+/-84 h. CONCLUSION: This four-step protocol may promote medical decision making on end-of-life care.

Do we need a systematic activation of alarm soundings for blood pressure monitoring for the safety of ICU patients?

PURPOSE: Evaluation of a protocol of activation-deactivation of alarm soundings on noninvasive mean arterial pressure (MAP) monitoring. MATERIALS AND METHODS: 103 patients were analyzed. Alarm soundings on noninvasive MAP were either activated (group A) or inactivated (group NA) according to a protocol based on patient's hemodynamic status. RESULTS: In the first part of the study (11 periods of 24 hours), we informed the nursing staff before data collection. In the second part of the study (11 periods of 24 hours), we did not inform the nursing staff before data collection. Results of the two parts were assembled and the final analysis consisted of 3,304 hours of monitoring with 12,839 noninvasive MAP measurements, 6,354 in group A and 6,485 in group NA. In group A, 75 of 944 (8%) of abnormal measurements were detected or managed with a delay > 15 minutes and among them 16 required a therapeutic adjustment. In group NA, 140 of 265 (53%) of abnormal measurements were detected or managed with a delay > 15 minutes and among them, only one required a therapeutic adjustment. The number of alarm soundings avoided in group NA was 286. CONCLUSION: In this study, a systematic activation of alarm soundings for non-invasive blood pressure monitoring seemed unnecessary for the safety of ICU patients.

A five-step protocol for withholding and withdrawing of life support in an emergency department: an observational study.

OBJECTIVE: The objective of the study was to describe a five-step protocol for withholding and withdrawing of life support (WH/WDLS) in an emergency department (ED) for terminally ill patients. DESIGN AND SETTING: An observational study was conducted in ED of a general hospital. PATIENTS: A total of 98 patients were admitted over a 1-year period. INTERVENTIONS: The healthcare team chose a pattern of treatment limitation on the basis of a five-step protocol for every patient, which comprised five groups: group 1: there was no limitation of care, group 2: do not resuscitate order was followed, group 3: administration of therapies without treating an acute organ failure, group 4: active withdrawal of all therapies except mechanical ventilation and group 5: active withdrawal of mechanical ventilation. All the patients received comfort care. The opinions of the patients and their families were collected. MEASUREMENTS AND RESULTS: Ninety-eight patients were included in the study (1.5% of admissions). Mean age was 82+/-13 years. An acute organ failure was observed at admission in 80 patients. Severe chronic disease was noted in 93 patients. Among the 98 patients, there were 14 patients in group 2, 65 in group 3, six in group 4 and 13 in group 5. The time interval between admission and WH/WDLS decision was 117+/-77 min and ED stay was 239+/-136 min. The outcome was death in ED (n=21), admission to a medical ward (n=71) or an intensive care unit (n=six). On day 30, 16 patients were still alive. CONCLUSION: This five-step protocol could improve collaboration in the WH/WDLS decision-making process, while facilitating dialogue and transmission of information between staff and families.

Administration of the nitric oxide synthase inhibitor NG-methyl-L-arginine hydrochloride (546C88) by intravenous infusion for up to 72 hours can promote the resolution of shock in patients with severe sepsis: results of a randomized, double-blind, placebo-controlled multicenter study (study no. 144-002).

OBJECTIVE: To assess the safety and efficacy of the nitric oxide synthase inhibitor 546C88 in patients with septic shock. The predefined primary efficacy objective was resolution of shock, defined as a mean arterial pressure > or =70 mm Hg in the absence of both conventional vasopressors and study drug, determined at the end of the 72-hr treatment period. DESIGN: Multicentered, randomized, placebo-controlled, safety and efficacy study. SETTING: Forty-eight intensive care units in Europe, North America, and Australia. PATIENTS: A total of 312 patients with septic shock diagnosed within 24 hr before randomization. INTERVENTIONS: Patients were randomly allocated to receive either 546C88 or placebo (5% dextrose) by intravenous infusion for up to 72 hrs. Conventional vasoactive therapy was restricted to norepinephrine, dopamine, and dobutamine. Study drug was initiated at 0.1 mL/kg/hr (5 mg/kg/hr 546C88) and titrated according to response up to a maximum rate of 0.4 mL/kg/hr with the objective to maintain mean arterial pressure at 70 mm Hg while attempting to withdraw any concurrent vasopressor(s). MEASUREMENTS AND MAIN RESULTS: Requirement for vasopressors, systemic hemodynamics, indices of organ function and safety (including survival up to day 28) were assessed. The median mean arterial pressure for both groups was maintained >70 mm Hg. Administration of 546C88 was associated with a decrease in cardiac index while stroke index was maintained. Resolution of shock at 72 hr was achieved by 40% and 24% of the patients in the 546C88 and placebo cohorts, respectively (p =.004). There was no evidence that treatment with 546C88 had any major adverse effect on pulmonary, hepatic, or renal function. Day 28 survival was similar for both groups. CONCLUSIONS: In this study, treatment with the nitric oxide synthase inhibitor 546C88 promoted the resolution of shock in patients with severe sepsis. This was associated with an acceptable overall safety profile.

Multiple-center, randomized, placebo-controlled, double-blind study of the nitric oxide synthase inhibitor 546C88: effect on survival in patients with septic shock.

OBJECTIVE: To assess the safety and efficacy of the nitric oxide synthase inhibitor 546C88 in patients with septic shock. The predefined primary efficacy objective was survival at day 28. DESIGN: Multiple-center, randomized, two-stage, double-blind, placebo-controlled, safety and efficacy study. SETTING: A total of 124 intensive care units in Europe, North America, South America, South Africa, and Australasia. PATIENTS: A total of 797 patients with septic shock diagnosed for <24 hrs. INTERVENTIONS: Patients with septic shock were allocated to receive 546C88 or placebo (5% dextrose) for up to 7 days (stage 1) or 14 days (stage 2) in addition to conventional therapy. Study drug was initiated at 0.05 mL.kg(-1).hr(-1) (2.5 mg.kg(-1).hr(-1) 546C88) and titrated up to a maximum rate of 0.4 mL.kg(-1).hr(-1) to maintain mean arterial pressure between 70 and 90 mm Hg while attempting to withdraw concurrent vasopressors. MEASUREMENTS AND MAIN RESULTS: Hemodynamic variables, organ function data, microbiological data, concomitant therapy, and adverse event data were recorded at baseline, throughout treatment, and at follow-up. The primary end point was day-28 survival. The trial was stopped early after review by the independent data safety monitoring board. Day-28 mortality was 59% (259/439) in the 546C88 group and 49% (174/358) in the placebo group (p <.001). The overall incidence of adverse events was similar in both groups, although a higher proportion of the events was considered possibly attributable to study drug in the 546C88 group. Most of the events accounting for the disparity between the groups were associated with the cardiovascular system (e.g., decreased cardiac output, pulmonary hypertension, systemic arterial hypertension, heart failure). The causes of death in the study were consistent with those expected in patients with septic shock, although there was a higher proportion of cardiovascular deaths and a lower incidence of deaths caused by multiple organ failure in the 546C88 group. CONCLUSIONS: In this study, the nonselective nitric oxide synthase inhibitor 546C88 increased mortality in patients with septic shock.