21 May 06
Posted in Critical Care, Mechanical ventilation, Sedation at 9:57 by Laci
By PS Richman, D Baram, M Varela, P Glass
Critical Care Medicine 2006;34:1395-1401
Objective
To compare the efficacy of continuous intravenous sedation with midazolam alone vs. midazolam plus fentanyl (“co-sedation”) during mechanical ventilation.
Design
A randomized, prospective, controlled trial.
Setting
A ten-bed medical intensive care unit at a university hospital.
Patients
Thirty patients with respiratory failure who were expected to require >48 hrs of mechanical ventilation and who were receiving a sedative regimen that did not include opiate pain control.
Interventions
An intravenous infusion of either midazolam alone or co-sedation was administered by a nurse-implemented protocol to achieve a target Ramsay Sedation Score set by the patient’s physician. Study duration was 3 days, with a brief daily “wake-up.”
Measurements and Main Results
We recorded the number of hours/day that patients were “off-target” with their Ramsay Sedation Scores, the number of dose titrations per day, the incidence of patient-ventilator asynchrony, and the time required to achieve adequate sedation as measures of sedative efficacy. We also recorded sedative cost in U.S. dollars and adverse events including hypotension, hypoventilation, ileus, and coma. Compared with the midazolam-only group, the co-sedation group had fewer hours per day with an “off-target” Ramsay Score (4.2 +/- 2.4 and 9.1 +/- 4.9, respectively, p < .002). Fewer episodes per day of patient-ventilator asynchrony were noted in the co-sedation group compared with midazolam-only (0.4 +/- 0.1 and 1.0 +/- 0.2, respectively, p < .05). Co-sedation also showed nonsignificant trends toward a shorter time to achieve sedation, a need for fewer dose titrations per day, and a lower total sedative drug cost. There was a trend toward more episodes of ileus with co-sedation compared with midazolam-only (2 vs. 0).
Conclusions
In mechanically ventilated patients, co-sedation with midazolam and fentanyl by constant infusion provides more reliable sedation and is easier to titrate than midazolam alone, without significant difference in the rate of adverse events.
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Posted in Critical Care at 9:56 by Laci
By X Monnet, M Rienzo, D Osman, N Anguel, C Richard, M Pinsky et al
Critical Care Medicine 2006;34:1402-1407
Objective
Passive leg raising (PLR) represents a “self-volume challenge” that could predict fluid response and might be useful when the respiratory variation of stroke volume cannot be used for that purpose. We hypothesized that the hemodynamic response to PLR predicts fluid responsiveness in mechanically ventilated patients.
Design
Prospective study.
Setting
Medical intensive care unit of a university hospital.
Patients
We investigated 71 mechanically ventilated patients considered for volume expansion. Thirty-one patients had spontaneous breathing activity and/or arrhythmias.
Interventions
We assessed hemodynamic status at baseline, after PLR, and after volume expansion (500 mL NaCl 0.9% infusion over 10 mins).
Measurements and Main Results
We recorded aortic blood flow using esophageal Doppler and arterial pulse pressure. We calculated the respiratory variation of pulse pressure in patients without arrhythmias. In 37 patients (responders), aortic blood flow increased by >=15% after fluid infusion. A PLR increase of aortic blood flow >=10% predicted fluid responsiveness with a sensitivity of 97% and a specificity of 94%. A PLR increase of pulse pressure >=12% predicted volume responsiveness with significantly lower sensitivity (60%) and specificity (85%). In 30 patients without arrhythmias or spontaneous breathing, a respiratory variation in pulse pressure >=12% was of similar predictive value as was PLR increases in aortic blood flow (sensitivity of 88% and specificity of 93%). In patients with spontaneous breathing activity, the specificity of respiratory variations in pulse pressure was poor (46%).
Conclusions
The changes in aortic blood flow induced by PLR predict preload responsiveness in ventilated patients, whereas with arrhythmias and spontaneous breathing activity, respiratory variations of arterial pulse pressure poorly predict preload responsiveness.
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20 May 06
Posted in rhAPC, Sepsis, Venous thromboembolism at 11:39 by Laci
Sepsis Late-Breaker: the EVBR Study
By Derek Angus, Frank Booth, Michael Matthay, Marcel Levi
SCCM 35th Critical Care Congress: Sepsis Late-Breaker. Presented Jan. 11, 2006. San Francisco
The Xigris and Prophylactic Heparin in Severe Sepsis (XPRESS) study was a phase 4 trial mandated by the FDA after subanalysis of the Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis (PROWESS) trial suggested that heparin reduced the efficacy of drotrecogin.
The landmark PROWESS trial showed a significant decrease in mortality in severe sepsis with drotrecogin.
XPRESS was a multicenter, international study of approximately 1900 patients with severe sepsis who were receiving drotrecogin and at high risk for death. Patients were randomized to 1 of 3 treatment groups: mechanical thromboprophylaxis, unfractionated heparin, or low-molecular-weight heparin (enoxaparin) given in standard doses during the 96-hour drotrecogin infusion period.
Principal investigator Mitchell Levy, MD, FCCM, professor of medicine and director of the medical intensive care unit at Brown University in Providence, Rhode Island, delivered the findings. The primary end point was 28-day all-cause mortality. Secondary end points were any thrombotic event and safety and efficacy of the drug combination.
Twenty-eight-day mortality was unchanged in the 2 groups. Neither was the incidence of thrombotic events significantly different between the 2 groups, (drotrecogin plus heparin, 4.6% vs 5.1% in the control group. This was true both during the 96-hour infusion period and after 28 days of follow-up.
The primary end point of efficacy was similar between study and control groups of the study, with an absolute mortality rate of 31% across treatment groups after 28 days of follow-up. “In this high-risk group, that mortality rate is quite good,” Dr. Levy asserted.
“We are unable to conclude from this study whether drotrecogin plus heparin is any better than drotrecogin alone,” Dr. Levy noted. “This study was not designed to show that. What we can say is that physicians can safely add heparin without fear of a loss of efficacy with drotrecogin” in patients at high risk of deep vein thrombosis. Estimates show that approximately 85% to 90% of patients in intensive care units receive prophylactic heparin.
Because of the severity of their illness — often on mechanical ventilation and immobile — patients in this subgroup are also given heparin for thromboprophylaxis. “Heparin should be used in high-risk patients and PROWESS supports that,” Dr. Ely asserted.
Mark William, MD, associate medical director of the Xigris Product Team at Eli Lilly, told Mescape that “we can now reject the FDA hypothesis that adding heparin to [drotrecogin] reduces its efficacy…. What we found, though, was that if a patient was on heparin at the time [drotrecogin] was initiated, it was important for the patient to stay on it. Mortality was higher if heparin was stopped and restarted after [drotrecogin] was begun.”
Dr. Williams added that the combination of the 2 drugs did not result in a higher incidence of serious adverse effects, including bleeding, although the incidence of minor bleeding was increased in patients receiving dual therapy.
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Posted in Critical Care, Inotropic support at 9:56 by Laci
By SM Lobo, FR Lobo, CA Polachini, DS Patini, AE Yamamoto, NE de Oliveira et al
Critical Care 2006;10:R72
Preventing perioperative tissue oxygen debt contributes to a better postoperative recovery. Whether the beneficial effects of fluids and inotropes during optimization of the oxygen delivery index (DO2I) in high-risk patients submitted to major surgeries are due to fluids, to inotropes, or to the combination of the two is not known. We aimed to investigate the effect of DO2I optimization with fluids or with fluids and dobutamine on the 60-day hospital mortality and incidence of complications.
Methods
A randomized and controlled trial was performed in 50 high-risk patients (elderly with coexistent pathologies) undergoing major elective surgery. Therapy consisted of pulmonary artery catheter-guided hemodynamic optimization during the operation and 24 hours postoperatively using either fluids alone (n = 25) or fluids and dobutamine (n = 25), aiming to achieve supranormal values (DO2I > 600 ml/minute/m2).
Results
The cardiovascular depression was an important component in the perioperative period in this group of patients. Cardiovascular complications in the postoperative period occurred significantly more frequently in the volume group (13/25, 52%) than in the dobutamine group (4/25, 16%) (relative risk, 3.25; 95% confidence interval, 1.22–8.60; P < 0.05). The 60-day mortality rates were 28% in the volume group and 8% in the dobutamine group (relative risk, 3.00; 95% confidence interval, 0.67–13.46; not significant).
Conclusion
In patients with high risk of perioperative death, pulmonary artery catheter-guided hemodynamic optimization using dobutamine determines better outcomes, whereas fluids alone increase the incidence of postoperative complications.
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