Remifentanil/midazolam versus fentanyl/midazolam for analgesia and sedation of mechanically ventilated neonates and young infants: a randomized controlled trial

Purpose

Common opioids for analgesia and sedation of mechanically ventilated infants may tend to accumulate and cause prolonged sedation with an unpredictable extubation time. Remifentanil is a promising option due to its unique pharmacokinetic properties, which seem to be valid in adults as well as in infants.

Methods

In this double-blind, randomized, controlled trial mechanically ventilated neonates and young infants (<60?days) received either a remifentanil or fentanyl-based analgesia and sedation regimen with low dose midazolam. The primary endpoint of the trial was the extubation time following discontinuation of the opioid infusion. Secondary endpoints included efficacy and safety aspects.

Results

Between November 2006 and March 2010, we screened 431 mechanically ventilated infants for eligibility. The intention to treat group included 23 infants who were assigned to receive either remifentanil (n?=?11) or fentanyl (n?=?12). Although this was designed as a pilot study, median extubation time was significantly shorter in the remifentanil group (80.0?min, IQR?=?15.0–165.0) compared to the fentanyl group (782.5?min, IQR?=?250.8–1,875.0) (p?=?0.005). Remifentanil and fentanyl provided comparable efficacy with more than two-thirds of the measurements indicating optimal analgesia and sedation (66.4 and 70.2?%, respectively; p?=?0.743). Overall, both groups had good hemodynamic stability and a comparably low incidence of adverse events.

Conclusions

As neonates and young infants have a decreased metabolism of common opioids like fentanyl and are more prone to respiratory depression, remifentanil could be the ideal opioid for analgesia and sedation of mechanically ventilated infants.     

Outcome of critically ill lung transplant candidates on invasive respiratory support

Purpose

Lung transplantation (LTx) of patients on mechanical ventilation (MV) or extracorporeal support (ECS) is controversial because of impaired survival. Prognostic factors to predict survival should be identified.

Methods

A retrospective analysis was performed in a single centre of all ventilated LTx-candidates awarded an Eurotransplant (ET) high-urgency (HU) status between November 2004 and July 2009. Clinical data were collected on the first day of HU-status from intubated patients with an approved HU status. Single parameters as well as the lung allocation score (LAS), the Sequential Organ Failure Assessment score (SOFA) and the Simplified Acute Physiology Score (SAPS 2) were calculated. The association of these variables with survival was evaluated.

Results

A total of 100 intubated patients (median age 38?years, 56?% female) fulfilled the inclusion criteria, of whom 60 also required ECS. The main indications were cystic fibrosis (25?%) and idiopathic pulmonary fibrosis (24?%). Median time with HU status was 12?days [interquartile range (IQR) 6–21 days]. Sixty patients were transplanted, five were weaned from mechanical ventilation and 38 died while on the wait list. One-year-survival rates were 57, 36 and 5?% for transplanted patients, all candidates and non-transplanted candidates, respectively (p?24 (median 30, IQR 27–35), a procalcitonin level of >0.5?μg/l (median 0.4, IQR 0.1–1.4?μg/l) and any escalation of bridging strategy were independently associated with mortality (p = 0.021, = 0.003, and?p = 0.92).

Conclusions

High-urgency LTx improves survival in critically ill intubated candidates. Higher SAPS scores, escalating therapy and an abnormal procalcitonin level were associated with a poor outcome.     

Patient–ventilator synchrony and sleep quality with proportional assist and pressure support ventilation

Objective

To examine patient–ventilator asynchrony and sleep quality in non-sedated critically ill patients ventilated with proportional assist ventilation with load adjustable gain factors (PAV+) and pressure support (PSV).

Methods

This was a randomized crossover physiological study conducted in an adult ICU at a tertiary hospital. Patients who exhibited patient–ventilator asynchrony on PSV were selected. Polysomnography was performed in these patients over 24 h, during which respiratory variables were continuously recorded. During the study period, each patient was randomized to receive alternating 4-h periods of PSV and PAV+ equally distributed during the day and night. Sleep architecture was analyzed manually using predetermined criteria. Patient–ventilator asynchrony was evaluated breath by breath using the flow–time and airway pressure–time waveforms.

Results

Fourteen patients were studied. The majority (85.7 %) had either acute exacerbation of COPD as admission diagnosis or COPD as comorbidity. During sleep, compared to PSV, PAV+ significantly reduced the patient–ventilator asynchrony events per hour of sleep [5 (1–17) vs. 40 (4–443), p = 0.02, median (25–75th interquartile range)]. Compared to PSV, PAV+ was associated with slightly but significantly greater sleep fragmentation [18.8 (13.1–33.1) versus 18.1 (7.0–22.8) events/h, p = 0.01] and less REM sleep [0.0 % (0.0–8.4) vs. 5.8 % (0.0–21.9), p = 0.02).

Conclusions

PAV+ failed to improve sleep in mechanically ventilated patients despite the fact that this mode was associated with better synchrony between the patient and ventilator. These results do not support the hypothesis that patient–ventilator synchrony plays a central role in determining sleep quality in this group of patients.     

Dexmedetomidine use in the ICU: Are we there yet?

Expanded abstract

Citation

Jakob SM, Ruokonen E, Grounds RM, Sarapohja T, Garratt C, Pocock SJ, Bratty JR, Takala J; Dexmedeto midine for Long-Term Sedation Investigators: Dexmedetomidine vesus midazolam or propofol for sedation during prolonged mechanical ventilation: two randomized controlled trials. JAMA 2012, 307:1151-1160.

Background

Long-term sedation with midazolam or propofol in intensive care units (ICUs) has serious adverse effects. Dexmedetomidine, an alpha-2 agonist available for ICU sedation, may reduce the duration of mechanical ventilation and enhance patient comfort.

Methods

Objective

The objective was to determine the efficacy of dexmedetomidine versus midazolam or propofol (preferred usual care) in maintaining sedation, reducing duration of mechanical ventilation, and improving patients'' interaction with nursing care.

Design

Two phase 3 multicenter, randomized, double-blind trials were conducted.

Setting

The MIDEX (Midazolam vs. Dexmedetomidine) trial compared midazolam with dexmedetomidine in ICUs of 44 centers in nine European countries. The PRODEX (Propofol vs. Dexmedetomidine) trial compared propofol with dexmedetomidine in 31 centers in six European countries and two centers in Russia.

Subjects

The subjects were adult ICU patients who were receiving mechanical ventilation and who needed light to moderate sedation for more than 24 hours.

Intervention

After enrollment, 251 and 249 subjects were randomly assigned midazolam and dexmedetomidine, respectively, in the MIDEX trial, and 247 and 251 subjects were randomly assigned propofol and dexmedetomidine, respectively, in the PRODEX trial. Sedation with dexmedetomidine, midazolam, or propofol; daily sedation stops; and spontaneous breathing trials were employed.

Outcomes

For each trial, investigators 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 the ability of the patient to communicate pain (measured by using a visual analogue scale [VAS]) and length of ICU stay. Time at target sedation was analyzed in per-protocol (midazolam, n = 233, versus dexmedetomidine, n = 227; propofol, n = 214, versus dexmedetomidine, n = 223) population.

Results

Dexmedetomidine/midazolam ratio in time at target sedation was 1.07 (95% confidence interval (CI) 0.97 to 1.18), and dexmedetomidine/propofol ratio in time at target sedation was 1.00 (95% CI 0.92 to 1.08). Median duration of mechanical ventilation appeared shorter with dexmedetomidine (123 hours, interquartile range (IQR) 67 to 337) versus midazolam (164 hours, IQR 92 to 380; P = 0.03) but not with dexmedetomidine (97 hours, IQR 45 to 257) versus propofol (118 hours, IQR 48 to 327; P = 0.24). Patient interaction (measured by using VAS) was improved with dexmedetomidine (estimated score difference versus midazolam 19.7, 95% CI 15.2 to 24.2; P <0.001; and versus propofol 11.2, 95% CI 6.4 to 15.9; P <0.001). Lengths of ICU and hospital stays and mortality rates were similar. Dexmedetomidine versus midazolam patients had more hypotension (51/247 [20.6%] versus 29/250 [11.6%]; P = 0.007) and bradycardia (35/247 [14.2%] versus 13/250 [5.2%]; P <0.001).

Conclusions

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 the ability of patients to communicate pain compared with midazolam and propofol. Greater numbers of adverse effects were associated with dexmedetomidine.     

Effects of propofol on sleep quality in mechanically ventilated critically ill patients: a physiological study

Purpose

To access the effect of propofol administration on sleep quality in critically ill patients ventilated on assisted modes.

Methods

This was a randomized crossover physiological study conducted in an adult ICU at a tertiary hospital. Two nights’ polysomnography was performed in mechanically ventilated critically ill patients with and without propofol infusion, while respiratory variables were continuously recorded. Arterial blood gasses were measured in the beginning and at the end of the study. The rate of propofol infusion was adjusted to maintain a sedation level of 3 on the Ramsay scale. Sleep architecture was analyzed manually using predetermined criteria. Patient–ventilator asynchrony was evaluated breath by breath using the flow–time and airway pressure–time waveforms.

Results

Twelve patients were studied. Respiratory variables, patient–ventilator asynchrony, and arterial blood gasses did not differ between experimental conditions. With or without propofol all patients demonstrated abnormal sleep architecture, expressed by lack of sequential progression through sleep stages and their abnormal distribution. Sleep efficiency, sleep fragmentation, and sleep stage distribution (1, 2, and slow wave) did not differ with or without propofol. Compared to without propofol, both the number of patients exhibiting REM sleep (p?=?0.02) and the percentage of REM sleep (p?=?0.04) decreased significantly with propofol.

Conclusions

In critically ill patients ventilated on assisted modes, propofol administration to achieve the recommended level of sedation suppresses the REM sleep stage and further worsens the poor sleep quality of these patients.     

Perioperative amplitude-integrated EEG and neurodevelopment in infants with congenital heart disease

Purpose

Perioperative brain injury is common in young infants undergoing cardiac surgery. We aimed to determine the relationship between perioperative electrical seizures, the background pattern of amplitude-integrated electroencephalography (aEEG) and 2-year neurodevelopmental outcome in young infants undergoing surgery for congenital heart disease.

Methods

A total of 150 newborn infants undergoing cardiac surgery underwent aEEG monitoring prior to and during surgery, and for 72?h postoperatively. Two blinded assessors reviewed the aEEGs for seizure activity and background pattern. Survivors underwent neurodevelopmental outcome assessment using the Bayley Scales of Infant Development (3rd edn.) at 2?years.

Results

The median age at surgery was 7?days (IQR 4–11). Cardiopulmonary bypass was used in 83?%. Perioperative electrical seizures occurred in 30?%, of whom 1/4 had a clinical correlate, but were not associated with 2-year outcome. Recovery to a continuous background occurred at a median 6 (3–13)?h and sleep–wake cycling recovered at 21 (14–30)?h. Prolonged aEEG recovery was associated with increased mortality and worse neurodevelopmental outcome. Failure of the aEEG to recover to a continuous background by 48?postoperative hours was associated with impairment in all outcome domains (p?p?Conclusions Perioperative seizures were common in this cohort of infants but did not impact on 2-year neurodevelopmental outcome. Delayed recovery in aEEG background was associated with increased risk of early mortality and worse neurodevelopment. Ongoing monitoring of the survivors is essential to determine the longer-term significance of these findings.     

Pharmacokinetics of prolonged infusion of high-dose dexmedetomidine in critically ill patients

Introduction

Only limited information exists on the pharmacokinetics of prolonged (> 24 hours) and high-dose dexmedetomidine infusions in critically ill patients. The aim of this study was to characterize the pharmacokinetics of long dexmedetomidine infusions and to assess the dose linearity of high doses. Additionally, we wanted to quantify for the first time in humans the concentrations of H-3, a practically inactive metabolite of dexmedetomidine.

Methods

Thirteen intensive care patients with mean age of 57 years and Simplified Acute Physiology Score (SAPS) II score of 45 were included in the study. Dexmedetomidine infusion was commenced by using a constant infusion rate for the first 12 hours. After the first 12 hours, the infusion rate of dexmedetomidine was titrated between 0.1 and 2.5 μg/kg/h by using predefined dose levels to maintain sedation in the range of 0 to -3 on the Richmond Agitation-Sedation Scale. Dexmedetomidine was continued as long as required to a maximum of 14 days. Plasma dexmedetomidine and H-3 metabolite concentrations were measured, and pharmacokinetic variables were calculated with standard noncompartmental methods. Safety and tolerability were assessed by adverse events, cardiovascular signs, and laboratory tests.

Results

The following geometric mean values (coefficient of variation) were calculated: length of infusion, 92 hours (117%); dexmedetomidine clearance, 39.7 L/h (41%); elimination half-life, 3.7 hours (38%); and volume of distribution during the elimination phase, 223 L (35%). Altogether, 116 steady-state concentrations were found in 12 subjects. The geometric mean value for clearance at steady state was 53.1 L/h (55%). A statistically significant linear relation (r ² = 0.95; P < 0.001) was found between the areas under the dexmedetomidine plasma concentration-time curves and cumulative doses of dexmedetomidine. The elimination half-life of H-3 was 9.1 hours (37%). The ratio of AUC_0-∞ of H-3 metabolite to that of dexmedetomidine was 1.47 (105%), ranging from 0.29 to 4.4. The ratio was not statistically significantly related to the total dose of dexmedetomidine or the duration of the infusion.

Conclusions

The results suggest linear pharmacokinetics of dexmedetomidine up to the dose of 2.5 μg/kg/h. Despite the high dose and prolonged infusions, safety findings were as expected for dexmedetomidine and the patient population.

Trial Registration

ClinicalTrials.gov: NCT00747721     

Impact of respiration gating on image integration guided atrial fibrillation ablation

Background

Radiofrequency (RF) catheter ablation guided by electroanatomic mapping systems is an effective therapy for atrial fibrillation. However, it may be affected by respiration movements. The aim of this study was to determine the impact of respiratory gating on procedural parameters in patients undergoing catheter ablation of atrial fibrillation (AF).

Methods and results

One-hundred forty consecutive patients undergoing pulmonary vein isolation were admitted to study. Respiratory gating module (AccuResp algorithm, Carto3, Biosense Webster) was enabled in 70 patients and disabled in 70 patients during procedures. Successful pulmonary vein isolation and sinus rhythm were obtained in all patients. A significant reduction in total procedure times [median 77, interquartile range (IQR 66–95) min vs median 82 (IQR 72–104) min, p < 0.05] and fluoroscopy times [median 14 (IQR 9–17) min vs median 16 (IQR 12–22) min, p < 0.05] were observed in the respiratory gated group. Although ablation times (duration between the first and last ablation) were significantly shorter in respiratory gated group [median 37 (IQR 32–53) min vs median 48 (IQR 39–65) min, p < 0.05], total RF application durations were not different between two groups [median 1,554 (IQR 1,213–2,196) s vs median 1,802 (IQR 1,344–2,448) s, p = 0.11]. Difference in electroanatomical map reconstruction times was not significant [median 14 (IQR 12–16) min in gated group vs median 13 (IQR 10–18) min in nongated group, p = 0.19].

Conclusion

Respiratory gating significantly improves fluoroscopy and ablation times during electroanatomic mapping guided AF ablation. Respiratory gated maps may provide uninterrupted continuous ablation applications. Furthermore, using automatic respiratory gating module does not prolong mapping times.     

Predictive value of bronchoscopy after infant cardiac surgery: a prospective study

Background and aims

Airway evaluation following infant cardiac surgery often reveals evidence of tracheobronchial narrowing. We studied the association between airway narrowing and extubation failure (EF) in this population.

Methods

Prospective cohort study of infants (age ≤6?months) from March–September 2009. Flexible bronchoscopy (FB) evaluations were obtained using a standardised protocol after operative intervention. The primary endpoint was the development of extubation failure (EF; defined as the need for invasive mechanical ventilation ≤48?h after primary extubation) and several secondary endpoints.

Results

Fifty-three patients were evaluated at a median age of 81 [interquartile range (IQR) 13–164] days and weight of 4.2 (IQR 3.2–6.0) kg; 13 (25?%) of the patients had single ventricle palliations and two subsequently underwent heart transplantation. Significant airway narrowing was noted in 15 of 30 [50 %, 95 % confidence interval (CI) 31–69?%] patients who underwent FB; ten of the 53 patients (19 %, 95 %CI 10–32?%) subsequently developed EF. Narrowed airway calibre on bronchoscopy had a sensitivity and specificity of 50 % (95 %CI 28–71 %) and 50 % (95 %CI 28–71 %), respectively, for EF. The single greatest predictor of EF by univariate analysis was the need for preoperative ventilation [odds ratio (OR)?6.5, 95 %CI 1.3–33.2, p?=?0.03]. Patients with EF had a greater likelihood of intensive care readmission (OR?4.8, 95 %CI 1.1–21, p?<?0.04) during the same hospital admission.

Conclusions

Airway narrowing on FB is noted frequently after infant cardiac surgery. Overall assessment and presence of narrowing on bronchoscopy had poor sensitivity and specificity for EF in our cohort. Expert assessment of tracheobronchial narrowing on FB has poor to moderate inter-rater reliability.     

Early intervention on the outcomes in critically ill cancer patients admitted to intensive care units

Purpose

To determine whether earlier intervention was associated with decreased mortality in critically ill cancer patients admitted to an intensive care unit (ICU).

Methods

A retrospective observational study was performed of 199 critically ill cancer patients admitted to the ICU from the general ward between January 2010 and December 2010. A logistic regression model was used to adjust for potential confounding factors in the association between time to intervention and in-hospital mortality.

Results

In-hospital mortality was 52?%, with a median Simplified Acute Physiology Score 3 (SAPS 3) of 80 [interquartile range (IQR) 67–93], and a median Sequential Organ Failure Assessment (SOFA) score of 8 (IQR 5–11). Median time from physiological derangement to intervention (time to intervention) prior to ICU admission was 1.5 (IQR 0.6–4.3)?h. Median time to intervention was significantly shorter in survivors than in non-survivors (0.9 vs. 3.0?h; p?p?2/FiO₂ ratio. Even after adjusting for potential confounding factors, time to intervention was still significantly associated with hospital mortality (adjusted odds ratio 1.445, 95?% confidence interval 1.217–1.717).

Conclusions

Early intervention before ICU admission was independently associated with decreased in-hospital mortality in critically ill cancer patients admitted to the ICU.     

Nighttime sleep duration and risk of nonalcoholic fatty liver disease: the Dongfeng-Tongji prospective study

Background: To examine the association between self-reported nighttime sleep duration and nonalcoholic fatty liver disease (NAFLD) risk by comparing the incidence rates of NAFLD among healthy subjects with different sleep duration during the 5 years follow-up.

Methods: 8965 eligible NAFLD-free subjects with a mean age of 61.6 years (males, 43.4%) from Dongfeng-Tongji cohort study at baseline were enrolled in the study. Logistic regression analysis was used to estimate the association between sleep duration and incident NAFLD with potential confounders adjusted. Sleep duration was categorized into five groups:?<6?h, 6–7?h, 7–8?h, 8–9?h,?≥9?h.

Result: During the 5-years of follow-up, a total of 2,197 participants were newly diagnosed as NAFLD. Compared with those reported 7–8?h per day of nighttime sleep, the multivariable-adjusted odds ratio (95% confidence intervals) were 1.21 (1.07–1.38) for those who sleep 8–9?h/day, and 1.31 (1.13–1.52) for those who sleep over 9?h/day. However, no significant association was found with short nightly sleep duration (<7?h/day).

Conclusion: Long nighttime sleep duration was associated with a modestly increased risk of NAFLD in a middle-aged and elderly Chinese population.

• Key messages

• Long nighttime sleep duration was associated with a modestly increased risk of NAFLD in a middle-aged and elderly Chinese population.

• The effect of long nighttime sleep on the risk of incident NAFLD was attenuated greatly by body mass index (BMI) in men.

     

Accuracy of plethysmographic indices as predictors of fluid responsiveness in mechanically ventilated adults: a systematic review and meta-analysis

Purpose

To systematically review the accuracy of the variation in pulse oxymetry plethysmographic waveform amplitude (?POP) and the Pleth Variability Index (PVI) as predictors of fluid responsiveness in mechanically ventilated adults.

Methods

MEDLINE, Scopus and the Cochrane Database of Systematic Reviews were screened for clinical studies in which the accuracy of ?POP/PVI in predicting the hemodynamic response to a subsequent fluid bolus had been investigated. Random-effects meta-analysis was used to summarize the results. Data were stratified according to the amount of fluid bolus (large vs. small) and to the study index (?POP vs. PVI).

Results

Ten studies in 233 patients were included in this meta-analysis. All patients were in normal sinus rhythm. The pooled area under the receiver operating characteristic curve (AUC) for identification of fluid responders was 0.85 [95?% confidence interval (CI) 0.79–0.92]. Pooled sensitivity and specificity were 0.80 (95 % CI 0.74–0.85) and 0.76 (0.68–0.82), respectively. No heterogeneity was found within studies with the same amount of fluid bolus, nor between studies on ?POP and those on PVI. The AUC was significantly larger in studies with a large bolus amount than in those with a small bolus [0.92 (95 % CI 0.87–0.96) vs. 0.70 (0.62–0.79); p?p?=?0.08 and 0.86 (95 % CI 0.75–0.93) vs. 0.68 (0.56–0.77) (small bolus), p?=?0.02], respectively.

Conclusions

Based on our meta-analysis, we conclude that ?POP and PVI are equally effective for predicting fluid responsiveness in ventilated adult patients in sinus rhythm. Prediction is more accurate when a large fluid bolus is administered.     

Screening for obstructive sleep apnea in veterans with ischemic heart disease using a computer-based clinical decision-support system

Objectives

To assess the validity of a handheld clinical decision-support system (CDSS) in detecting obstructive sleep apnea (OSA) in veterans with ischemic heart disease against polysomnography (PSG) and to compare the diagnostic accuracy of the CDSS versus the Berlin questionnaire.

Methods

We enrolled prospectively 143 patients with underlying ischemic heart disease. Veterans with history of neurologic disease, systolic congestive heart failure, or receiving opiates were excluded from participation. Participants were asked to complete the Berlin Questionnaire and to answer all eight questions of CDSS-software. At the end of the interview, veterans were scheduled for an in-laboratory polysomnogram.

Results

Ninety one patients completed the study. The prevalence of OSA (AHI ≥5/h) was 74.7?% with a median AHI of 11.5/h (range 0–90). When compared to PSG, the CDSS and the Berlin questionnaire achieved a sensitivity of 98.5?% [95?% confidence interval (CI) 92.1–100] and 80.9?% (95?% CI 69.5–89.4) and a specificity of 86.9?% (95?% CI 66.4–97.2) and 39.1?% (95?% CI 19.7–61.5) at a threshold value of AHI ≥5 with a corresponding area under the curve of 0.93 (95?% CI 0.85–0.97) and 0.60 (95?% CI 0.49–0.70); respectively.

Conclusions

CDSS is a superior screening tool for identifying cardiac veterans with undiagnosed OSA than the BQ.     

A prospective randomised multi-centre controlled trial on tight glucose control by intensive insulin therapy in adult intensive care units: the Glucontrol study

Purpose

An optimal target for glucose control in ICU patients remains unclear. This prospective randomized controlled trial compared the effects on ICU mortality of intensive insulin therapy (IIT) with an intermediate glucose control.

Methods

Adult patients admitted to the 21 participating medico-surgical ICUs were randomized to group 1 (target BG 7.8–10.0 mmol/L) or to group 2 (target BG 4.4–6.1 mmol/L).

Results

While the required sample size was 1,750 per group, the trial was stopped early due to a high rate of unintended protocol violations. From 1,101 admissions, the outcomes of 542 patients assigned to group 1 and 536 of group 2 were analysed. The groups were well balanced. BG levels averaged in group 1 8.0 mmol/L (IQR 7.1–9.0) (median of all values) and 7.7 mmol/L (IQR 6.7–8.8) (median of morning BG) versus 6.5 mmol/L (IQR 6.0–7.2) and 6.1 mmol/L (IQR 5.5–6.8) for group 2 (p < 0.0001 for both comparisons). The percentage of patients treated with insulin averaged 66.2 and 96.3%, respectively. Proportion of time spent in target BG was similar, averaging 39.5% and 45.1% (median (IQR) 34.3 (18.5–50.0) and 39.3 (26.2–53.6)%) in the groups 1 and 2, respectively. The rate of hypoglycaemia was higher in the group 2 (8.7%) than in group 1 (2.7%, p < 0.0001). ICU mortality was similar in the two groups (15.3 vs. 17.2%).

Conclusions

In this prematurely stopped and therefore underpowered study, there was a lack of clinical benefit of intensive insulin therapy (target 4.4–6.1 mmol/L), associated with an increased incidence of hypoglycaemia, as compared to a 7.8–10.0 mmol/L target. (ClinicalTrials.gov # NCT00107601, EUDRA-CT Number: 200400391440).     

Estimation of mean systemic filling pressure in postoperative cardiac surgery patients with three methods

Purpose

To assess the level of agreement between different bedside estimates of effective circulating blood volume—mean systemic filling pressure (Pmsf), arm equilibrium pressure (Parm) and model analog (Pmsa)—in ICU patients.

Methods

Eleven mechanically ventilated postoperative cardiac surgery patients were studied. Sequential measures were made in the supine position, rotating the bed to a 30° head-up tilt and after fluid loading (500?ml colloid). During each condition four inspiratory hold maneuvers were done to determine Pmsf; arm stop-flow was created by inflating a cuff around the upper arm for 30?s to measure Parm, and Pmsa was estimated from a Guytonian model of the systemic circulation.

Results

Mean Pmsf, Parm and Pmsa across all three states were 20.9?±?5.6, 19.8?±?5.7 and 14.9?±?4.0?mmHg, respectively. Bland-Altman analysis for the difference between Parm and Pmsf showed a non-significant bias of ?1.0?±?3.08?mmHg (p?=?0.062), a coefficient of variation (COV) of 15?%, and limits of agreement (LOA) of ?7.3 and 5.2?mmHg. For the difference between Pmsf and Pmsa we found a bias of ?6.0?±?3.1?mmHg (p?Conclusions Parm and Pmsf are interchangeable in mechanically ventilated postoperative cardiac surgery patients. Changes in effective circulatory volume are tracked well by changes in Parm and Pmsa.     

Assist-control ventilation vs. low levels of pressure support ventilation on sleep quality in intubated ICU patients

Objective To compare the impact of assist-control ventilation (ACV) and pressure support ventilation with 6 cmH₂O inspiratory pressure (low PSV) on sleep quality. Design Prospective randomized cross-over study. Patients Twenty intubated and mechanically ventilated patients for acute on chronic respiratory failure. Measurements Patients were monitored by standard polysomnography at the end of their weaning period. Patients were assigned to receive either ACV from 10 p.m. to 2 a.m. and low PSV from 2 a.m. to 6 a.m. (ACV/low PSV group) or low PSV from 10 p.m. to 2 a.m. and ACV from 2 a.m. to 6 a.m. (low PSV/ACV group). Results There were significant increases in stages 1 and 2 non-rapid eye movement (NREM) sleep and reduction in wakefulness during the first part of the night and significant increases in stages 3 and 4 NREM sleep during the second part of the night were observed with ACV compared to low PSV. A significant negative correlation was observed between the perceived sleep quality and the amount of wakefulness while the amount of stage 2 NREM sleep was positively correlated with perceived sleep quality. Conclusions ACV was significantly associated with a better sleep quality than those recorded during pressure support. The perception of sleep quality appeared to be better with ACV than with low PSV. On the basis of these results we recommend that intubated and mechanically ventilated patients for acute on chronic respiratory failure should be reventilated at night during their weaning period.     

右美托咪定对老年危重症机械通气患者的镇静效果及对睡眠的影响

目的:探究右美托咪定对老年危重症机械通气患者的镇静效果及对睡眠的影响。方法:选取2019年12月至2021年7月东莞市水乡中心医院收治的需行机械通气的老年危重症患者120例作为研究对象,根据入院时间随机分为对照组和观察组,每组60例。对照组患者给予咪达唑仑联合舒芬太尼治疗,观察组患者给予右美托咪定联合舒芬太尼治疗;观察2组患者通气后不同时间节点HR、SBP、DBP和SpO₂水平,评估治疗后2组患者通气总时间、入住ICU时间、镇静效果和睡眠质量,记录不良反应反生情况。结果:观察组患者用药后6 h、12 h、24 h和48 h后HR、SBP、DBP和SpO₂水平显著优于对照组;观察组患者机械通气总时间和入住ICU时间均显著短于对照组,Ramsay和PSQI评分均显著低于对照组;观察组不良反应发生率(5.0%)显著低于对照(13.3%),差异均有统计学意义(均P<0.05)。结论:右美托咪定对老年危重症机械通气患者临床疗效确切,可显著提高患者的镇静效果和睡眠质量,值得推广应用。     

Incidence and risk factors for mortality in paediatric severe sepsis: results from the national paediatric intensive care registry in Japan

Purpose

To assess the incidence, background, outcome and risk factors for death of severe sepsis in Japanese paediatric intensive care units (PICUs).

Methods

A data analysis of a prospective, multicentre, 3-year case registry from nine medical-surgical Japanese PICUs. Children with severe sepsis, aged 0–15?years, who were consecutively admitted to the participating PICUs from 1 January 2007 to 31 December 2009 were enrolled. The incidence, background, causative pathogens or infective foci, outcome and risk factors for death caused by severe sepsis were analysed.

Results

One hundred forty-one cases were registered. After the exclusion of 14 patients because of incomplete data or inappropriate entry, 127 patients were eligible for the analysis. There were 60 boys and 67 girls, aged 23 [5–68] (median [IQR]) months and weighed 10 [5.5–16.5]?kg. The incidence was 1.4?% of total PICU admissions. Sepsis was community-acquired in 35?%, PICU-acquired in 37?% and acquired in hospital general wards in 28?%. Methicillin-resistant Staphylococcus aureus was the most frequent pathogen. The crude 28-day mortality was 18.9?%, comparable to the mean PIM-2 predicted mortality (17.7?%). The mortality rate in patients with shock was significantly increased to 28?% compared to those without shock (5?%). The presences of existing haematological disorders (OR 8.97, 95?% CI, 1.56–51.60) and shock (OR 5.35, 1.04–27.44) were significant factors associated with mortality by multivariate analysis.

Conclusions

The mortality from severe sepsis/septic shock in Japanese PICUs was?~19?%. Haematological disorders and presence of shock were associated with death.     

Physical restraint in mechanically ventilated ICU patients: a survey of French practice

Purpose

To characterize the perceived utilization of physical restraint (PR) in mechanically ventilated intensive care unit (ICU) patients and to identify clinical and structural factors influencing PR use.

Methods

A questionnaire was personally handed to one intensivist in 130 ICUs in France then collected on-site 2?weeks later.

Results

The questionnaire was returned by 121 ICUs (response rate, 93?%), 66?% of which were medical-surgical ICUs. Median patient-to-nurse ratio was 2.8 (2.5?C3.0). In 82?% of ICUs, PR is used at least once during mechanical ventilation in more than 50?% of patients. In 65?% of ICUs, PR, when used, is applied for more than 50?% of mechanical ventilation duration. Physical restraint is often used during awakening from sedation and when agitation occurs and is less commonly used in patients receiving deep sedation or neuromuscular blockers or having severe tetraparesis. In 29?% of ICUs, PR is used in more than 50?% of awake, calm and co-operative patients. PR is started without written medical order in more than 50?% of patients in 68?% of ICUs, and removed without written medical order in more than 50?% of patients in 77?% of ICUs. Only 21?% of ICUs have a written local procedure for PR use.

Conclusions

This survey in a country with a relatively high patient-to-nurse ratio shows that PR is frequently used in patients receiving mechanical ventilation, with wide variations according to patient condition. The common absence of medical orders for starting or removing PR indicates that these decisions are mostly made by the nurses.     

Is the volume of mechanically ventilated admissions to UK critical care units associated with improved outcomes?

Background

It is unknown whether a volume–outcome relationship exists for mechanically ventilated admissions to UK critical care units. This study was conducted to evaluate the volume–outcome relationship for mechanically ventilated admissions to adult, general critical care units in the UK with a view to informing policy, service delivery and organisation of specialist, advanced respiratory care.

Methods

A retrospective cohort study using data from the Case Mix Programme Database was conducted. The primary exposure of interest was annual volume (absolute number) of mechanically ventilated admissions per critical care unit per year. The primary outcome was ultimate acute hospital mortality. A multivariable analysis was performed to assess the relationship between annual volume and outcome while adjusting for a priori selected confounders. Two interaction tests were performed. The first interaction test was between annual volume and admission type and the second between annual volume and initial acute severity of respiratory failure. Sensitivity analysis excluding volume outlier units and using restricted cubic splines to model volume was also performed.

Results

After adjusting for confounding, there was a significant relationship between annual volume and ultimate acute hospital mortality (p < 0.02). The first interaction test revealed a strong interaction between annual volume and admission type, with a more pronounced volume–outcome relationship for non-surgical admissions (p < 0.001). The second interaction test between annual volume and initial acute severity of respiratory failure was not statistically significant (p = 0.12). The analysis using restricted cubic splines demonstrated a similar graphical relationship but the results were not statistically significant (p = 0.87).

Conclusions

A volume–outcome relationship was demonstrated for mechanically ventilated admissions to adult, general critical care units in the UK. The relationship is sensitive to the modelling approach used.