Platelet Transfusion before CVC Placement in Patients with Thrombocytopenia.

BACKGROUND: Transfusion guidelines regarding platelet-count thresholds before the placement of a central venous catheter (CVC) offer conflicting recommendations because of a lack of good-quality evidence. The routine use of ultrasound guidance has decreased CVC-related bleeding complications. METHODS: In a multicenter, randomized, controlled, noninferiority trial, we randomly assigned patients with severe thrombocytopenia (platelet count, 10,000 to 50,000 per cubic millimeter) who were being treated on the hematology ward or in the intensive care unit to receive either one unit of prophylactic platelet transfusion or no platelet transfusion before ultrasound-guided CVC placement. The primary outcome was catheter-related bleeding of grade 2 to 4; a key secondary outcome was grade 3 or 4 bleeding. The noninferiority margin was an upper boundary of the 90% confidence interval of 3.5 for the relative risk. RESULTS: We included 373 episodes of CVC placement involving 338 patients in the per-protocol primary analysis. Catheter-related bleeding of grade 2 to 4 occurred in 9 of 188 patients (4.8%) in the transfusion group and in 22 of 185 patients (11.9%) in the no-transfusion group (relative risk, 2.45; 90% confidence interval [CI], 1.27 to 4.70). Catheter-related bleeding of grade 3 or 4 occurred in 4 of 188 patients (2.1%) in the transfusion group and in 9 of 185 patients (4.9%) in the no-transfusion group (relative risk, 2.43; 95% CI, 0.75 to 7.93). A total of 15 adverse events were observed; of these events, 13 (all grade 3 catheter-related bleeding [4 in the transfusion group and 9 in the no-transfusion group]) were categorized as serious. The net savings of withholding prophylactic platelet transfusion before CVC placement was $410 per catheter placement. CONCLUSIONS: The withholding of prophylactic platelet transfusion before CVC placement in patients with a platelet count of 10,000 to 50,000 per cubic millimeter did not meet the predefined margin for noninferiority and resulted in more CVC-related bleeding events than prophylactic platelet transfusion. (Funded by ZonMw; PACER Dutch Trial Register number, NL5534.).

Sex difference and intra-operative tidal volume: Insights from the LAS VEGAS study.

BACKGROUND: One key element of lung-protective ventilation is the use of a low tidal volume (VT). A sex difference in use of low tidal volume ventilation (LTVV) has been described in critically ill ICU patients. OBJECTIVES: The aim of this study was to determine whether a sex difference in use of LTVV also exists in operating room patients, and if present what factors drive this difference. DESIGN, PATIENTS AND SETTING: This is a posthoc analysis of LAS VEGAS, a 1-week worldwide observational study in adults requiring intra-operative ventilation during general anaesthesia for surgery in 146 hospitals in 29 countries. MAIN OUTCOME MEASURES: Women and men were compared with respect to use of LTVV, defined as VT of 8 ml kg-1 or less predicted bodyweight (PBW). A VT was deemed 'default' if the set VT was a round number. A mediation analysis assessed which factors may explain the sex difference in use of LTVV during intra-operative ventilation. RESULTS: This analysis includes 9864 patients, of whom 5425 (55%) were women. A default VT was often set, both in women and men; mode VT was 500 ml. Median [IQR] VT was higher in women than in men (8.6 [7.7 to 9.6] vs. 7.6 [6.8 to 8.4] ml kg-1 PBW, P < 0.001). Compared with men, women were twice as likely not to receive LTVV [68.8 vs. 36.0%; relative risk ratio 2.1 (95% CI 1.9 to 2.1), P < 0.001]. In the mediation analysis, patients' height and actual body weight (ABW) explained 81 and 18% of the sex difference in use of LTVV, respectively; it was not explained by the use of a default VT. CONCLUSION: In this worldwide cohort of patients receiving intra-operative ventilation during general anaesthesia for surgery, women received a higher VT than men during intra-operative ventilation. The risk for a female not to receive LTVV during surgery was double that of males. Height and ABW were the two mediators of the sex difference in use of LTVV. TRIAL REGISTRATION: The study was registered at Clinicaltrials.gov, NCT01601223.

The effects of preoperative moderate to severe anaemia on length of hospital stay: A propensity score-matched analysis in non-cardiac surgery patients.

BACKGROUND: Anaemia is frequently recorded during preoperative screening and has been suggested to affect outcomes after surgery negatively. OBJECTIVES: The objectives were to assess the frequency of moderate to severe anaemia and its association with length of hospital stay. DESIGN: Post hoc analysis of the international observational prospective 'Local ASsessment of VEntilatory management during General Anaesthesia for Surgery' (LAS VEGAS) study. PATIENTS AND SETTING: The current analysis included adult patients requiring general anaesthesia for non-cardiac surgery. Preoperative anaemia was defined as a haemoglobin concentration of 11 g dl-1 or lower, thus including moderate and severe anaemia according to World Health Organisation criteria. MAIN OUTCOME MEASURES: The primary outcome was length of hospital stay. Secondary outcomes included hospital mortality, intra-operative adverse events and postoperative pulmonary complications (PPCs). RESULTS: Haemoglobin concentrations were available for 8264 of 9864 patients. Preoperative moderate to severe anaemia was present in 7.7% of patients. Multivariable analysis showed that preoperative moderate to severe anaemia was associated with an increased length of hospital stay with a mean difference of 1.3 ((95% CI 0.8 to 1.8) days; P < .001). In the propensity-matched analysis, this association remained present, median 4.0 [IQR 1.0 to 5.0] vs. 2.0 [IQR 0.0 to 5.0] days, P = .001. Multivariable analysis showed an increased in-hospital mortality (OR 2.9 (95% CI 1.1 to 7.5); P  = .029), and higher incidences of intra-operative hypotension (36.3 vs. 25.3%; P < .001) and PPCs (17.1 vs. 10.5%; P = .001) in moderately to severely anaemic patients. However, this was not confirmed in the propensity score-matched analysis. CONCLUSIONS: In this international cohort of non-cardiac surgical patients, preoperative moderate to severe anaemia was associated with a longer duration of hospital stay but not increased intra-operative complications, PPCs or in-hospital mortality. TRIAL REGISTRATION: The LAS VEGAS study was registered at Clinicaltrials.gov, NCT01601223.

Potential of Parameters of Iron Metabolism for the Diagnosis of Anemia of Inflammation in the Critically Ill.

BACKGROUND: Anemia of inflammation (AI) is the most common cause of anemia in the critically ill, but its diagnosis is a challenge. New therapies specific to AI are in development, and they require accurate detection of AI. This study explores the potential of parameters of iron metabolism for the diagnosis of AI during an ICU stay. METHODS: In a nested case-control study, 30 patients developing AI were matched to 60 controls. The iron parameters were determined in plasma samples during an ICU stay. Receiver operating characteristic curves were used to determine the iron parameter threshold with the highest sensitivity and specificity to predict AI. Likelihood ratios as well as positive and negative predictive values were calculated as well. RESULTS: The sensitivity of iron parameters for diagnosing AI ranges between 62 and 76%, and the specificity between 57 and 72%. Iron and transferrin show the greatest area under the curve. Iron shows the highest sensitivity, and transferrin and transferrin saturation display the highest specificity. Hepcidin and ferritin show the lowest specificity. At an actual anemia prevalence of 53%, the diagnostic accuracy of iron, transferrin, and transferrin saturation was fair, with a positive predictive value between 71 and 73%. Combining iron, transferrin, transferrin saturation, hepcidin, and/or ferritin levels did not increase the accuracy of the AI diagnosis. CONCLUSIONS: In this explorative study on the use of different parameters of iron metabolism for diagnosing AI during an ICU stay, low levels of commonly measured markers such as plasma iron, transferrin, and transferrin saturation have the highest sensitivity and specificity and outperform ferritin and hepcidin.

On-demand versus continuous rocuronium infusion for deep neuromuscular relaxation in patients undergoing thoraco-laparoscopic esophagectomy: a randomized-controlled clinical trial (DEPTH).

PURPOSE: Deep neuromuscular blockade (NMB) can improve surgical conditions and possibly pain after low-risk laparoscopic surgery. We hypothesized that targeting a deep level of NMB by a continuous compared with an on-demand infusion of rocuronium could improve surgical conditions in patients undergoing thoraco-laparoscopic esophagectomy. METHODS: In this single-centre, randomized-controlled, double-blind trial, patients received either a continuous infusion of rocuronium 0.6 mg·kg-1·hr-1 (intervention) or NaCl 0.9% (control). Both surgeon and anesthesiologist were blinded to group assignment and the train-of-four measurements. Open-label rocuronium was given if requested (i.e., on-demand) by the surgeon. At the end of surgery, sugammadex was given if necessary to reverse the NMB. The primary outcome was the quality of surgical conditions during the abdominal phase of the operation as measured by the surgical rating scale (SRS). Secondary outcomes included the thoracic SRS, number of on-demand boluses, intraoperative surgical events, pain scores (up to 12 hr postoperatively), and duration of surgery. RESULTS: The median [interquartile range] abdominal SRS was not different between the intervention (4 [4-5]) and control (4 [4-5]) groups (median difference, 0; 95% confidence interval, 0 to 0; P = 0.45). The thoracic SRS was 4 [4-4] in both groups (P = 0.23). The median number of rocuronium bolus requests was higher in the control group compared with the intervention group (3 [3-6] vs 1 [0-2], respectively; P < 0.01). There were no between-group differences in intraoperative surgical events (P = 0.05), pain scores (overall P > 0.05), or duration of surgery (P = 0.95). CONCLUSIONS: Continuous rocuronium infusion did not improve surgical conditions when boluses of rocuronium were available on-demand. No major benefits in other outcomes were seen. TRIAL REGISTRATION: EUDRACT (2014-002147-18); registered 19 May, 2014 and clinicaltrials.gov (NCT02320734); registered 18 December, 2014.

Respiratory Viruses in Invasively Ventilated Critically Ill Patients-A Prospective Multicenter Observational Study.

OBJECTIVES: The presence of respiratory viruses and the association with outcomes were assessed in invasively ventilated ICU patients, stratified by admission diagnosis. DESIGN: Prospective observational study. SETTING: Five ICUs in the Netherlands. PATIENTS: Between September 1, 2013, and April 30, 2014, 1,407 acutely admitted and invasively ventilated patients were included. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Nasopharyngeal swabs and tracheobronchial aspirates were collected upon intubation and tested for 14 respiratory viruses. Out of 1,407 patients, 156 were admitted because of a severe acute respiratory infection and 1,251 for other reasons (non-severe acute respiratory infection). Respiratory viruses were detected in 28.8% of severe acute respiratory infection patients and 17.0% in non-severe acute respiratory infection (p < 0.001). In one third, viruses were exclusively detected in tracheobronchial aspirates. Rhinovirus and human metapneumovirus were more prevalent in severe acute respiratory infection patients (9.6% and 2.6% vs 4.5 and 0.2%; p = 0.006 and p < 0.001). In both groups, there were no associations between the presence of viruses and the number of ICU-free days at day 28, crude mortality, and mortality in multivariate regression analyses. CONCLUSIONS: Respiratory viruses are frequently detected in acutely admitted and invasively ventilated patients. Rhinovirus and human metapneumovirus are more frequently found in severe acute respiratory infection patients. Detection of respiratory viruses is not associated with worse clinically relevant outcomes in the studied cohort of patients.

Incidence, risk factors, and outcome of transfusion-associated circulatory overload in a mixed intensive care unit population: a nested case-control study.

BACKGROUND: The objective of this study was to determine the incidence, risk factors, and outcome of transfusion-associated circulatory overload (TACO) in a cohort of mixed intensive care unit patients and to compare risk factors with those for cardiac overload in the absence of transfusion. STUDY DESIGN AND METHODS: In a retrospective cohort study, patients who developed TACO were compared using multivariate analysis of two control groups: patients without pulmonary deterioration who received transfusion and patients who developed circulatory overload in the absence of transfusion. RESULTS: TACO was diagnosed in 66 of 1140 patients who received transfusions (5.8%). A total of 585 control transfusion recipients and 76 control patients who developed circulatory overload also were identified. Risk factors were the referring specialties cardiology (odds ratio [OR], 13.6; 95% confidence interval [CI], 5.1-35.7; p ≤ 0.001) and cardiothoracic surgery (OR, 8.8; 95% CI, 3.7-20.7; p ≤ 0.001), history of cardiac failure (OR, 2.4; 95% CI, 1.2-4.6; p = 0.01), continuous veno-venous hemofiltration (OR, 3.2; 95% CI, 1.2-8.9; p = 0.03), and degree of positive fluid balance (OR, 1.15; 95% CI, 1.07-1.24; p ≤ 0.001), which was associated less with the onset of TACO compared with circulatory overload (OR, 0.89; 95% CI, 0.82-0.97; p = 0.005). Patients in the TACO group had a longer length of stay in the intensive care unit compared with the transfusion and circulatory overload controls groups (median, 7.2 vs. 4.3 vs. 4.4 days; p = 0.001 vs. p = 0.008). CONCLUSIONS: The incidence of TACO is high in a mixed intensive care unit population. The risk factors identified for TACO are cardiac failure, renal failure, and degree of positive fluid balance. A positive fluid balance may be less essential in the onset of TACO than in the onset of circulatory overload in the absence of transfusion.

Effect of a Low vs Intermediate Tidal Volume Strategy on Ventilator-Free Days in Intensive Care Unit Patients Without ARDS: A Randomized Clinical Trial.

Importance: It remains uncertain whether invasive ventilation should use low tidal volumes in critically ill patients without acute respiratory distress syndrome (ARDS). Objective: To determine whether a low tidal volume ventilation strategy is more effective than an intermediate tidal volume strategy. Design, Setting, and Participants: A randomized clinical trial, conducted from September 1, 2014, through August 20, 2017, including patients without ARDS expected to not be extubated within 24 hours after start of ventilation from 6 intensive care units in the Netherlands. Interventions: Invasive ventilation using low tidal volumes (n = 477) or intermediate tidal volumes (n = 484). Main Outcomes and Measures: The primary outcome was the number of ventilator-free days and alive at day 28. Secondary outcomes included length of ICU and hospital stay; ICU, hospital, and 28- and 90-day mortality; and development of ARDS, pneumonia, severe atelectasis, or pneumothorax. Results: In total, 961 patients (65% male), with a median age of 68 years (interquartile range [IQR], 59-76), were enrolled. At day 28, 475 patients in the low tidal volume group had a median of 21 ventilator-free days (IQR, 0-26), and 480 patients in the intermediate tidal volume group had a median of 21 ventilator-free days (IQR, 0-26) (mean difference, -0.27 [95% CI, -1.74 to 1.19]; P = .71). There was no significant difference in ICU (median, 6 vs 6 days; 0.39 [-1.09 to 1.89]; P = .58) and hospital (median, 14 vs 15 days; -0.60 [-3.52 to 2.31]; P = .68) length of stay or 28-day (34.9% vs 32.1%; hazard ratio [HR], 1.12 [0.90 to 1.40]; P = .30) and 90-day (39.1% vs 37.8%; HR, 1.07 [0.87 to 1.31]; P = .54) mortality. There was no significant difference in the percentage of patients developing the following adverse events: ARDS (3.8% vs 5.0%; risk ratio [RR], 0.86 [0.59 to 1.24]; P = .38), pneumonia (4.2% vs 3.7%; RR, 1.07 [0.78 to 1.47]; P = .67), severe atelectasis (11.4% vs 11.2%; RR, 1.00 [0.81 to 1.23]; P = .94), and pneumothorax (1.8% vs 1.3%; RR, 1.16 [0.73 to 1.84]; P = .55). Conclusions and Relevance: In patients in the ICU without ARDS who were expected not to be extubated within 24 hours of randomization, a low tidal volume strategy did not result in a greater number of ventilator-free days than an intermediate tidal volume strategy. Trial Registration: ClinicalTrials.gov Identifier: NCT02153294.

Effect of On-Demand vs Routine Nebulization of Acetylcysteine With Salbutamol on Ventilator-Free Days in Intensive Care Unit Patients Receiving Invasive Ventilation: A Randomized Clinical Trial.

Importance: It remains uncertain whether nebulization of mucolytics with bronchodilators should be applied for clinical indication or preventively in intensive care unit (ICU) patients receiving invasive ventilation. Objective: To determine if a strategy that uses nebulization for clinical indication (on-demand) is noninferior to one that uses preventive (routine) nebulization. Design, Setting, and Participants: Randomized clinical trial enrolling adult patients expected to need invasive ventilation for more than 24 hours at 7 ICUs in the Netherlands. Interventions: On-demand nebulization of acetylcysteine or salbutamol (based on strict clinical indications, n = 471) or routine nebulization of acetylcysteine with salbutamol (every 6 hours until end of invasive ventilation, n = 473). Main Outcomes and Measures: The primary outcome was the number of ventilator-free days at day 28, with a noninferiority margin for a difference between groups of -0.5 days. Secondary outcomes included length of stay, mortality rates, occurrence of pulmonary complications, and adverse events. Results: Nine hundred twenty-two patients (34% women; median age, 66 (interquartile range [IQR], 54-75 years) were enrolled and completed follow-up. At 28 days, patients in the on-demand group had a median 21 (IQR, 0-26) ventilator-free days, and patients in the routine group had a median 20 (IQR, 0-26) ventilator-free days (1-sided 95% CI, -0.00003 to ∞). There was no significant difference in length of stay or mortality, or in the proportion of patients developing pulmonary complications, between the 2 groups. Adverse events (13.8% vs 29.3%; difference, -15.5% [95% CI, -20.7% to -10.3%]; P < .001) were more frequent with routine nebulization and mainly related to tachyarrhythmia (12.5% vs 25.9%; difference, -13.4% [95% CI, -18.4% to -8.4%]; P < .001) and agitation (0.2% vs 4.3%; difference, -4.1% [95% CI, -5.9% to -2.2%]; P < .001). Conclusions and Relevance: Among ICU patients receiving invasive ventilation who were expected to not be extubated within 24 hours, on-demand compared with routine nebulization of acetylcysteine with salbutamol did not result in an inferior number of ventilator-free days. On-demand nebulization may be a reasonable alternative to routine nebulization. Trial Registration: clinicaltrials.gov Identifier: NCT02159196.

Incorporation of Daily Goals in Daily Care Planning Does Not Shorten Length of Stay in the Intensive Care Unit.

A strategy of defining and checking explicitly formulated patient-specific treatments targets or "daily goals" in the intensive care unit has been associated with improved communication. We investigated the effect of incorporation of daily goals into daily care planning on length of stay in the intensive care unit. Furthermore, the type of daily goals and deviations from daily goals in daily care with or without documented reason were evaluated. Four university hospitals in the Netherlands, of which 2 study "daily goal" hospitals and 2 control hospitals, participated in a prospective before-after study. During the before phase of the study, daily goals were formulated by the attending physician but kept blinded from doctors and nurses caring for the patient. During the after phase of the study, daily goals were integrated in the care plan for patients admitted to the 2 study hospitals but not for patients admitted to the control hospitals. The implementation of daily goals was, after case-mix correction, not associated with a change in intensive care unit length of stay. However, this study showed that an improved administrative discipline, that is, the recording of the reason why a daily goal or standard protocol was not accomplished, is in favor of the daily goal implementation.

Central venous catheter placement in coagulopathic patients: risk factors and incidence of bleeding complications.

BACKGROUND: Central venous catheters are frequently inserted into patients with coagulation disorders. It is unclear whether preprocedural correction of hemostasis is beneficial. We determined the incidence of bleeding complications after central venous catheter placement in patients who had severe coagulopathy and identified potential risk factors for bleeding. STUDY DESIGN AND METHODS: The MEDLINE and Cochrane Library databases were systematically searched through November 2015. To be included, articles must have reported on hemorrhagic complications with specification of abnormal coagulation testing results. Severe coagulopathy was defined as a reduced platelet count of 50 × 109 /L or less, and/or an elevated international normalized ratio of 1.5 or greater, and/or a partial thromboplastin time of 45 seconds or greater. RESULTS: We included one randomized controlled trial and 21 observational studies. In total, there were 13,256 catheter insertions, including 4213 in patients with severe coagulopathy. Before 3150 central venous catheter placements, coagulopathy was not corrected. The bleeding incidence varied from 0 to 32%. The severity of coagulopathy did not predict the risk of bleeding. No study demonstrated a beneficial effect from the prophylactic administration of platelets or fresh-frozen plasma to prevent bleeding complications. Retrospective observational studies suggested that no preprocedural correction is required up to a platelet count of 20 × 109 /L and an international normalized ratio of 3.0. CONCLUSION: The incidence of major bleeding complications after central venous catheter placement is low, even in coagulopathic patients. Based on a systematic research of the literature, strong evidence supporting the correction of hemostatic defects before central venous catheter insertion is lacking. However, well-powered randomized controlled trials will be necessary to determine the minimal platelet count, the maximal international normalized ratio, and an activated partial thromboplastin time that is safe before central venous catheter insertion.

Impact of Positive End-Expiratory Pressure on Thermodilution-Derived Right Ventricular Parameters in Mechanically Ventilated Critically Ill Patients.

OBJECTIVES: To examine the effect of positive end-expiratory pressure (PEEP) on right ventricular stroke volume variation (SVV), with possible implications for the number and timing of pulmonary artery catheter thermodilution measurements. DESIGN: Prospective, clinical pilot study. SETTING: Academic medical center. PARTICIPANTS: Patients who underwent volume-controlled mechanical ventilation and had a pulmonary artery catheter. INTERVENTION: PEEP was increased from 5-to-10 cmH2O and from 10-to-15 cmH2O with 10-minute intervals, with similar decreases in PEEP, from 15-to-10 cmH2O and 10-to-5 cmH2O. MEASUREMENTS AND MAIN RESULTS: In 15 patients, right ventricular parameters were measured using thermodilution at 10% intervals of the ventilatory cycle at each PEEP level with a rapid-response thermistor. Mean right ventricular stroke volume and end-diastolic volume declined during incremental PEEP and normalized on return to 5 cmH2O PEEP (p = 0.01 and p = 0.001, respectively). Right ventricular SVV remained unaltered by changes in PEEP (p = 0.26), regardless of incremental PEEP (p = 0.15) or decreased PEEP (p = 0.12). The coefficients of variation in the ventilatory cycle of all other thermodilution-derived right ventricular parameters also were unaffected by changes in PEEP. CONCLUSIONS: This study showed that increases in PEEP did not affect right ventricular SVV in critically ill patients undergoing mechanical ventilation despite reductions in mean right ventricular stroke volume and end-diastolic volume. This could be explained by cyclic counteracting changes in right ventricular preloading and afterloading during the ventilatory cycle, independent of PEEP. Changes in PEEP did not affect the number and timing of pulmonary artery catheter thermodilution measurements.

Guideline implementation powered by feedback and education improves manual hyperinflation performance.

AIM: To determine whether a literature-based guideline, powered by educational meetings and individual feedback, improves manual hyperinflation (MH) performance by intensive care unit (ICU) nurses. BACKGROUND: MH is frequently applied in intubated and mechanically ventilated ICU patients. MH is a complex intervention, and large variation in its performance has been found. MATERIALS AND METHODS: First, a literature-based guideline on MH was developed. The intervention consisted of education of this guideline and individual feedback. Before and 3 months after the intervention, ICU nurses performed MH maneuvers in a skills laboratory. Data collected included applied volumes, peak inspiratory flows (PIF) and peak expiratory flows (PEF), and the use of inspiratory holds. RESULTS: Eighty nurses participated. Decrease of PIF was not statistically significant. PEF increased from 52 ± 7 to 83 ± 23 L/min (P < 0·01). PIF to PEF ratio decreased from 1·4 [1·1-1·7] to 0·8 [0·6-1·1] (P < 0·01). Peak inspiratory pressures decreased from 40 ± 14 to 19 ± 6 cm H2 O (P < 0·01). The proportion of nurses applying inspiratory holds increased from 14% to 58%; use of rapid release of the resuscitation bag, considered mandatory, increased from 4% to 61%. CONCLUSION: Implementation of a literature-based guideline on MH, powered by educational meetings and individual feedback, improves MH performance by ICU nurses. RELEVANCE TO CLINICAL PRACTICE: If it is decided to practice MH in the care of the intubated and mechanical ventilated patient, a standardized, uniform performed MH procedure is a prerequisite.

Low-risk transfusion-related acute lung injury donor strategies and the impact on the onset of transfusion-related acute lung injury: a meta-analysis.

BACKGROUND: Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion-related mortality. In the past decade blood banks have implemented low-risk TRALI donor strategies, including a male-only donor policy for plasma-containing blood products to prevent onset of TRALI. We performed a meta-analysis to determine whether use of low-risk TRALI donor strategies for plasma indeed reduces onset of TRALI. STUDY DESIGN AND METHODS: We searched MEDLINE and Cochrane Central Register of Controlled Trials from January 1995 up to January 2013. Two reviewers independently extracted data on study characteristics, methods, and outcomes. Primary endpoint was onset of TRALI. Subgroup analyses were performed for patient populations prone to develop TRALI and general patient populations. RESULTS: Ten articles were included. Meta-analysis using a random-effects model taking into account all transfused products showed a significant reduction for the risk of TRALI after implementation of low-risk TRALI donor strategies (odds ratio [OR], 0.61; 95% confidence interval [CI], 0.42-0.88). Data from patient populations prone to develop TRALI showed a significant reduction of TRALI risk (OR, 0.51; 95% CI, 0.29-0.90), while data from general patient populations showed a similar nonsignificant trend (OR, 0.66; 95% CI, 0.40-1.09). Results were similar when taking only plasma products into account (OR, 0.62; 95% CI, 0.42-0.92). CONCLUSION: The introduction of low-risk TRALI donor strategies for plasma-containing products results in a reduction of TRALI.

Transfusion of fresh-frozen plasma in critically ill patients with a coagulopathy before invasive procedures: a randomized clinical trial (CME).

BACKGROUND: Prophylactic use of fresh-frozen plasma (FFP) is common practice in patients with a coagulopathy undergoing an invasive procedure. Evidence that FFP prevents bleeding is lacking, while risks of transfusion-related morbidity after FFP have been well demonstrated. We aimed to assess whether omitting prophylactic FFP transfusion in nonbleeding critically ill patients with a coagulopathy who undergo an intervention is noninferior to a prophylactic transfusion of FFP. STUDY DESIGN AND METHODS: A multicenter randomized open-label trial with blinded endpoint evaluation was performed in critically ill patients with a prolonged international normalized ratio (INR; 1.5-3.0). Patients undergoing placement of a central venous catheter, percutaneous tracheostomy, chest tube, or abscess drainage were eligible. Patients with clinically overt bleeding, thrombocytopenia, or therapeutic use of anticoagulants were excluded. Patients were randomly assigned to omitting or administering a prophylactic transfusion of FFP (12 mL/kg). Outcomes were occurrence of postprocedural bleeding complications, INR correction, and occurrence of lung injury. RESULTS: Due to slow inclusion, the trial was stopped before the predefined target enrollment was reached. Eighty-one patients were randomly assigned, 40 to FFP and 41 to no FFP transfusion. Incidence of bleeding did not differ between groups, with a total of one major and 13 minor bleedings (p = 0.08 for noninferiority). FFP transfusion resulted in a reduction of INR to less than 1.5 in 54% of transfused patients. No differences in lung injury scores were observed. CONCLUSION: In critically ill patients undergoing an invasive procedure, no difference in bleeding complications was found regardless whether FFP was prophylactically administered or not.

Protective versus Conventional Ventilation for Surgery: A Systematic Review and Individual Patient Data Meta-analysis.

BACKGROUND: Recent studies show that intraoperative mechanical ventilation using low tidal volumes (VT) can prevent postoperative pulmonary complications (PPCs). The aim of this individual patient data meta-analysis is to evaluate the individual associations between VT size and positive end-expiratory pressure (PEEP) level and occurrence of PPC. METHODS: Randomized controlled trials comparing protective ventilation (low VT with or without high levels of PEEP) and conventional ventilation (high VT with low PEEP) in patients undergoing general surgery. The primary outcome was development of PPC. Predefined prognostic factors were tested using multivariate logistic regression. RESULTS: Fifteen randomized controlled trials were included (2,127 patients). There were 97 cases of PPC in 1,118 patients (8.7%) assigned to protective ventilation and 148 cases in 1,009 patients (14.7%) assigned to conventional ventilation (adjusted relative risk, 0.64; 95% CI, 0.46 to 0.88; P < 0.01). There were 85 cases of PPC in 957 patients (8.9%) assigned to ventilation with low VT and high PEEP levels and 63 cases in 525 patients (12%) assigned to ventilation with low VT and low PEEP levels (adjusted relative risk, 0.93; 95% CI, 0.64 to 1.37; P = 0.72). A dose-response relationship was found between the appearance of PPC and VT size (R2 = 0.39) but not between the appearance of PPC and PEEP level (R2 = 0.08). CONCLUSIONS: These data support the beneficial effects of ventilation with use of low VT in patients undergoing surgery. Further trials are necessary to define the role of intraoperative higher PEEP to prevent PPC during nonopen abdominal surgery.

Point accuracy and reliability of an interstitial continuous glucose-monitoring device in critically ill patients: a prospective study.

INTRODUCTION: There is a need for continuous glucose monitoring in critically ill patients. The objective of this trial was to determine the point accuracy and reliability of a device designed for continuous monitoring of interstitial glucose levels in intensive care unit patients. METHODS: We evaluated point accuracy by comparing device readings with glucose measurements in arterial blood by using blood gas analyzers. Analytical and clinical accuracy was expressed in Bland-Altman plots, glucose prediction errors, and Clarke error grids. We used a linear mixed model to determine which factors affect the point accuracy. In addition, we determined the reliability, including duration of device start-up and calibration, skips in data acquisition, and premature disconnections of sensors. RESULTS: We included 50 patients in whom we used 105 sensors. Five patients from whom we could not collect the predefined minimum number of four consecutive comparative blood draws were excluded from the point accuracy analysis. Therefore, we had 929 comparative samples from 100 sensors in 45 patients (11 (7 to 28) samples per patient) during 4,639 hours (46 (27 to 134) hours per patient and 46 (21 to 69) hours per sensor) for the accuracy analysis. Point accuracy did not meet the International Organization for Standardization (ISO) 14971 standard for insulin dosing accuracy but did improve with increasing numbers of calibrations and was better in patients who did not have a history of diabetes. Out of 105 sensors, 60 were removed prematurely for a variety of reasons. The device start-up time was 49 (43 to 58) minutes. The number of skips in data acquisition was low, resulting in availability of real-time data during 95% (89% to 98%) of the connection time per sensor. CONCLUSIONS: The point accuracy of a device designed for continuous real-time monitoring of interstitial glucose levels was relatively low in critically ill patients. The device had few downtimes, but one third of the sensors were removed prematurely because of unresolved sensor- or device-related problems. TRIAL REGISTRATION: Netherlands Trial Registry number: NTR3827 . Registered 30 January 2013.

Thromboelastometry and organ failure in trauma patients: a prospective cohort study.

INTRODUCTION: Data on the incidence of a hypercoagulable state in trauma, as measured by thromboelastometry (ROTEM), is limited and the prognostic value of hypercoagulability after trauma on outcome is unclear. We aimed to determine the incidence of hypercoagulability after trauma, and to assess whether early hypercoagulability has prognostic value on the occurrence of multiple organ failure (MOF) and mortality. METHODS: This was a prospective observational cohort study in trauma patients who met the highest trauma level team activation. Hypercoagulability was defined as a G value of ≥ 11.7 dynes/cm(2) and hypocoagulability as a G value of <5.0 dynes/cm(2). ROTEM was performed on admission and 24 hours later. RESULTS: A total of 1,010 patients were enrolled and 948 patients were analyzed. Median age was 38 (interquartile range (IQR) 26 to 53), 77% were male and median injury severity score was 13 (IQR 8 to 25). On admission, 7% of the patients were hypercoagulable and 8% were hypocoagulable. Altogether, 10% of patients showed hypercoagulability within the first 24 hours of trauma. Hypocoagulability, but not hypercoagulability, was associated with higher sequential organ failure assessment scores, indicating more severe MOF. Mortality in patients with hypercoagulability was 0%, compared to 7% in normocoagulable and 24% in hypocoagulable patients (P <0.001). EXTEM CT, alpha and G were predictors for occurrence of MOF and mortality. CONCLUSIONS: The incidence of a hypercoagulable state after trauma is 10% up to 24 hours after admission, which is broadly comparable to the rate of hypocoagulability. Further work in larger studies should define the clinical consequences of identifying hypercoagulability and a possible role for very early, targeted use of anticoagulants.

Prognosis of coma after therapeutic hypothermia: a prospective cohort study.

OBJECTIVE: This study was designed to establish the reliability of neurologic examination, neuron-specific enolase (NSE), and median nerve somatosensory-evoked potentials (SEPs) to predict poor outcome in patients treated with mild hypothermia after cardiopulmonary resuscitation (CPR). METHODS: This multicenter prospective cohort study included adult comatose patients admitted to the intensive care unit (ICU) after CPR and treated with hypothermia (32-34°C). False-positive rates (FPRs 1 - specificity) with their 95% confidence intervals (CIs) were calculated for pupillary light responses, corneal reflexes, and motor scores 72 hours after CPR; NSE levels at admission, 12 hours after reaching target temperature, and 36 hours and 48 hours after collapse; and SEPs during hypothermia and after rewarming. The primary outcome was poor outcome, defined as death, vegetative state, or severe disability (Glasgow Outcome Scale 1-3) after 6 months. RESULTS: Of 391 patients included, 53% had a poor outcome. Absent pupillary light responses (FPR 1; 95% CI, 0-7) or absent corneal reflexes (FPR 4; 95% CI, 1-13) 72 hours after CPR, and absent SEPs during hypothermia (FPR 3; 95% CI, 1-7) and after rewarming (FPR 0; 95% CI, 0-18) were reliable predictors. Motor scores 72 hours after CPR (FPR 10; 95% CI, 6-16) and NSE levels were not. INTERPRETATION: In patients with persisting coma after CPR and therapeutic hypothermia, use of motor score or NSE, as recommended in current guidelines, could possibly lead to inappropriate withdrawal of treatment. Poor outcomes can reliably be predicted by testing brainstem reflexes 72 hours after CPR and performing SEP.

The incidence, risk factors, and outcome of transfusion-related acute lung injury in a cohort of cardiac surgery patients: a prospective nested case-control study.

Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion-related morbidity and mortality. Both antibodies and bioactive lipids that have accumulated during storage of blood have been implicated in TRALI pathogenesis. In a single-center, nested, case-control study, patients were prospectively observed for onset of TRALI according to the consensus definition. Of 668 patients, 16 patients (2.4%) developed TRALI. Patient-related risk factors for onset of TRALI were age and time on the cardiopulmonary bypass. Transfusion-related risk factors were total amount of blood products (odds ratio [OR] = 1.2; 95% confidence interval [CI], 1.03-1.44), number of red blood cells stored more than 14 days (OR = 1.6; 95% CI, 1.04-2.37), total amount of plasma (OR = 1.2; 95% CI, 1.03-1.44), presence of antibodies in donor plasma (OR = 8.8; 95% CI, 1.8-44), and total amount of transfused bioactive lipids (OR = 1.0; 95% CI, 1.00-1.07). When adjusted for patient risk factors, only the presence of antibodies in the associated blood products remained a risk factor for TRALI (OR = 14.2; 95% CI, 1.5-132). In-hospital mortality of TRALI was 13% compared with 0% and 3% in transfused and nontransfused patients, respectively (P < .05). In conclusion, the incidence of TRALI is high in cardiac surgery patients and associated with adverse outcome. Our results suggest that cardiac surgery patients may benefit from exclusion of blood products containing HLA/HNA antibodies.