08 Apr 12
By S M Jakob, MD, E Ruokonen, R M Grounds, T Sarapohja, C Garratt, S J Pocock, J R Bratty, J Takala for the Dexmedetomidine for Long-Term Sedation Investigators
Long-term sedation with midazolam or propofol in intensive care units (ICUs) has serious adverse effects. Dexmedetomidine, an α2-agonist available for ICU sedation, may reduce the duration of mechanical ventilation and enhance patient comfort.
To determine the efficacy of dexmedetomidine vs midazolam or propofol (preferred usual care) in maintaining sedation; reducing duration of mechanical ventilation; and improving patients’ interaction with nursing care.
Design, setting, and patients
Two phase 3 multicenter, randomized, double-blind trials carried out from 2007 to 2010. The MIDEX trial compared midazolam with dexmedetomidine in ICUs of 44 centers in 9 European countries; the PRODEX trial compared propofol with dexmedetomidine in 31 centers in 6 European countries and 2 centers in Russia. Included were adult ICU patients receiving mechanical ventilation who needed light to moderate sedation for more than 24 hours (midazolam, n = 251, vs dexmedetomidine, n = 249; propofol, n = 247, vs dexmedetomidine, n = 251).
Sedation with dexmedetomidine, midazolam, or propofol; daily sedation stops; and spontaneous breathing trials.
Main outcome measures
For each trial, we tested whether dexmedetomidine was noninferior to control with respect to proportion of time at target sedation level (measured by Richmond Agitation-Sedation Scale) and superior to control with respect to duration of mechanical ventilation. Secondary end points were patients’ ability to communicate pain (measured using a visual analogue scale [VAS]) and length of ICU stay. Time at target sedation was analyzed in per-protocol population (midazolam, n = 233, vs dexmedetomidine, n = 227; propofol, n = 214, vs dexmedetomidine, n = 223).
Dexmedetomidine/midazolam ratio in time at target sedation was 1.07 (95% CI, 0.97-1.18) and dexmedetomidine/propofol, 1.00 (95% CI, 0.92-1.08). Median duration of mechanical ventilation appeared shorter with dexmedetomidine (123 hours [IQR, 67-337]) vs midazolam (164 hours [IQR, 92-380]; P = .03) but not with dexmedetomidine (97 hours [IQR, 45-257]) vs propofol (118 hours [IQR, 48-327]; P = .24). Patients’ interaction (measured using VAS) was improved with dexmedetomidine (estimated score difference vs midazolam, 19.7 [95% CI, 15.2-24.2]; P < .001; and vs propofol, 11.2 [95% CI, 6.4-15.9]; P < .001). Length of ICU and hospital stay and mortality were similar. Dexmedetomidine vs midazolam patients had more hypotension (51/247 [20.6%] vs 29/250 [11.6%]; P = .007) and bradycardia (35/247 [14.2%] vs 13/250 [5.2%]; P < .001).
Among ICU patients receiving prolonged mechanical ventilation, dexmedetomidine was not inferior to midazolam and propofol in maintaining light to moderate sedation. Dexmedetomidine reduced duration of mechanical ventilation compared with midazolam and improved patients’ ability to communicate pain compared with midazolam and propofol. More adverse effects were associated with dexmedetomidine.
24 Mar 10
By Y Wu , Y Tsai , C Lan , C Huang , C Lee , K Kao and J Fu
Critical Care 2010, 14:R26
Mechanical ventilation of patients may be accomplished by either translaryngeal intubation or tracheostomy. While numerous ICU studies have compared various outcomes between the two techniques, there is no definitive consensus that tracheostomy is superior. Comparable studies have not been performed in a respiratory care center (RCC) setting.
This was a retrospective observational study of 985 tracheostomy and 227 translaryngeal intubated patients who received treatment in a 24-bed RCC between November 1999 and December 2005. Treatment and mortality outcomes were compared between tracheostomized and translaryngeal intubated patients, and the factors associated with positive outcomes in all patients were determined.
Duration of RCC (22 vs. 14 days) and total hospital stay (82 vs. 64 days) and total mechanical ventilation days (53 vs. 41 days) were significantly longer in tracheostomized patients (all P<0.05). The rate of in-hospital mortality was significantly higher in the translaryngeal group (45% vs. 31%, P<0.05). There were no significant differences in weaning success between the groups (both were over 55%), nor RCC mortality. Due to significant baseline between group heterogeneity, case match analysis was performed. This analysis confirmed the whole cohort findings, except for the fact that there was only a trend for in-hospital mortality to be higher in the translaryngeal group (P=0.08). Stepwise logistic regression revealed that patients with a lower median severity of disease (APACHE II score <18) who were properly nourished (albumin >2.5 g/dL) or had normal metabolism (BUN <40 mg/dL) were more likely to be successfully weaned and survive (all P<0.05). Patients who were tracheostomized were also significantly more likely to survive (P<0.05)
These findings suggest that the type of mechanical ventilation does not appear to be an important determinant of weaning success in an RCC setting. Focused care administered by experienced providers may be more important for facilitating weaning success than the ventilation method used. However, our findings do suggest that tracheostomy may increase the likelihood of patient survival.
16 Mar 10
By T Strøm, T Martinussen, P Toft
The Lancet 2010;375:475-480
Standard treatment of critically ill patients undergoing mechanical ventilation is continuous sedation. Daily interruption of sedation has a benefi cial eff ect, and in the general intesive care unit of Odense University Hospital, Denmark, standard practice is a protocol of no sedation. We aimed to establish whether duration of mechanical ventilation could be reduced with a protocol of no sedation versus daily interruption of sedation.
Of 428 patients assessed for eligibility, we enrolled 140 critically ill adult patients who were undergoing mechanical ventilation and were expected to need ventilation for more than 24 h. Patients were randomly assigned in a 1:1 ratio (unblinded) to receive: no sedation (n=70 patients); or sedation (20 mg/mL propofol for 48 h, 1 mg/mL midazolam thereafter) with daily interruption until awake (n=70, control group). Both groups were treated with bolus doses of morphine (2·5 or 5 mg). The primary outcome was the number of days without mechanical ventilation in a 28-day period, and we also recorded the length of stay in the intensive care unit (from admission to 28 days) and in hospital (from admission to 90 days). Analysis was by intention to treat.
27 patients died or were successfully extubated within 48 h, and, as per our study design, were excluded from the study and statistical analysis. Patients receiving no sedation had signifi cantly more days without ventilation (n=55; mean 13·8 days, SD 11·0) than did those receiving interrupted sedation (n=58; mean 9·6 days, SD 10·0; mean diff erence 4·2 days, 95% CI 0·3–8·1; p=0·0191). No sedation was also associated with a shorter stay in the intensive care unit (HR 1·86, 95% CI 1·05–3·23; p=0·0316), and, for the fi rst 30 days studied, in hospital (3·57, 1·52–9·09; p=0·0039), than was interrupted sedation. No diff erence was recorded in the occurrences of accidental extubations, the need for CT or MRI brain scans, or ventilator-associated pneumonia. Agi tat ed delirium was more frequent in the intervention group than in the control group (n=11, 20% vs n=4, 7%; p=0·0400).
No sedation of critically ill patients receiving mechanical ventilation is associated with an increase in days without ventilation. A multicentre study is needed to establish whether this eff ect can be reproduced in other facilities.
20 Jan 10
By D Frankenfield, S Alam, E Bekteshi, R Vender
Crit Care Med 2010;38:288-291
To develop and validate an equation to predict dead space to tidal volume ratio (Vd/Vt) from clinically available data in critically ill mechanically ventilated patients.
Prospective, observational study using a convenience sample of patients whose arterial blood gas and respiratory gas exchange had been measured with indirect calorimetry.
Medical and surgical critical care units of a university medical center.
Adult, mechanically ventilated patients at rest with Fio2 ≤0.60 and no air leaks who had recent arterial blood gas recordings and end-tidal carbon dioxide concentration monitoring.
Measurements and main results
Indirect calorimetry was used to determine carbon dioxide production and expired minute ventilation in 135 patients. Tidal volume and respiratory rate were recorded from the ventilator. End tidal carbon dioxide concentration, body temperature, arterial carbon dioxide partial pressure (Paco2), and other clinical data were recorded. Vd/Vt was calculated using the Enghoff modification of the Bohr equation (Paco2 − PECO2/Paco2). Regression analysis was then used to construct a predictive equation for Vd/Vt using the clinical data: Vd/Vt = 0.32 + 0.0106 (Paco2 − ETCO2) + 0.003 (RR) + 0.0015 (age) (R2 = 0.67). A second group of 50 patients was measured using the same protocol and their data were used to validate the equations developed from the original 135 patients. The equation was found to be unbiased and precise.
Vd/Vt is predictable from clinically available data. Whether this predicted quantity is valuable clinically must still be determined.