Denise P. Veelo

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.

Fluid resuscitation with hydroxyethyl starches in patients with sepsis is associated with an increased incidence of acute kidney injury and use of renal replacement therapy: A systematic review and meta-analysis of the literature☆

PURPOSE Fluid resuscitation is a key intervention in sepsis, but the type of fluids used varies widely. The aim of this meta-analysis is to determine whether resuscitation with hydroxyethyl starches (HES) compared with crystalloids affects outcomes in patients with sepsis. MATERIALS AND METHODS Search of MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials up to February 2013. Studies that compared resuscitation with HES versus crystalloids in septic patients, and reported incidence of acute kidney injury (AKI), renal replacement therapy (RRT), transfusion of red blood cell (RBC) or fresh frozen plasma and/or mortality. Three investigators independently extracted data into uniform risk ratio measures. The Grading of Recommendations Assessment, Development and Evaluation framework was used to determine the quality of the evidence. RESULTS Ten trials (4624 patients) were included. An increased incidence of AKI (risk ratio [RR], 1.24 [95% Confidence Interval {CI}, 1.13-1.36], and need of RRT (RR, 1.36 [95% CI, 1.17-1.57]) was found in patients who received resuscitation with HES. Resuscitation with HES was also associated with increased transfusion of RBC (RR, 1.14 [95% CI, 1.01-1.93]), but not fresh frozen plasma (RR, 1.47 [95% CI, 0.97-2.24]). Furthermore, while intensive care unit mortality (RR, 0.74 [95% CI, 0.43-1.26]), and 28-day mortality (RR, 1.11 [95% CI, 0.96-1.28]) was not different, resuscitation with HES was associated with higher 90-day mortality (RR, 1.14 [95% CI, 1.04-1.26]). CONCLUSIONS Fluid resuscitation practice with HES as in the meta-analyzed studies is associated with increased an increase in AKI incidence, need of RRT, RBC transfusion, and 90-day mortality in patients with sepsis. Therefore, we favor the use of crystalloids over HES for resuscitation in patients with sepsis.

The safety and efficacy of irreversible electroporation for the ablation of prostate cancer: a multicentre prospective human in vivo pilot study protocol

Introduction Current surgical and ablative treatment options for prostate cancer have a relatively high incidence of side effects, which may diminish the quality of life. The side effects are a consequence of procedure-related damage of the blood vessels, bowel, urethra or neurovascular bundle. Ablation with irreversible electroporation (IRE) has shown to be effective in destroying tumour cells and harbours the advantage of sparing surrounding tissue and vital structures. The aim of the study is to evaluate the safety and efficacy and to acquire data on patient experience of minimally invasive, transperineally image-guided IRE for the focal ablation of prostate cancer. Methods and analysis In this multicentre pilot study, 16 patients with prostate cancer who are scheduled for a radical prostatectomy will undergo an IRE procedure, approximately 30 days prior to the radical prostatectomy. Data as adverse events, side effects, functional outcomes, pain and quality of life will be collected and patients will be controlled at 1 and 2 weeks post-IRE, 1 day preprostatectomy and postprostatectomy. Prior to the IRE procedure and the radical prostatectomy, all patients will undergo a multiparametric MRI and contrast-enhanced ultrasound of the prostate. The efficacy of ablation will be determined by whole mount histopathological examination, which will be correlated with the imaging of the ablation zone. Ethics and dissemination The protocol is approved by the ethics committee at the coordinating centre (Academic Medical Center (AMC) Amsterdam) and by the local Institutional Review Board at the participating centres. Data will be presented at international conferences and published in peer-reviewed journals. Conclusions This pilot study will determine the safety and efficacy of IRE in the prostate. It will show the radiological and histopathological effects of IRE ablations and it will provide data to construct an accurate treatment planning tool for IRE in prostate tissue. Trial registration number Clinicaltrials.gov database: NCT01790451.

Transfusion-related acute lung injury in cardiac surgery patients is characterized by pulmonary inflammation and coagulopathy: a prospective nested case-control study.

Objective: Transfusion-related acute lung injury is the leading cause of transfusion-related morbidity and mortality. Clinical data on the pathogenesis of transfusion-related acute lung injury are sparse. The objective of the present study was to determine inflammation and coagulation pathways involved in the onset of transfusion-related acute lung injury. Design: Nested case-control study. Setting: Operating theatre and intensive care department of a tertiary referral hospital. Patients: Elective cardiac surgery patients requiring postsurgery intensive care admission. Interventions: None. Measurements: Cardiac surgery patients (n = 668) were prospectively screened for the onset of transfusion-related acute lung injury. Transfusion-related acute lung injury cases (n = 16) were randomly assigned to transfused and nontransfused cardiac surgery controls in a 1:2 ratio. Blood samples were taken pre- and postoperatively and at onset of transfusion-related acute lung injury. In addition, at onset of transfusion-related acute lung injury, bronchoalveolar lavage fluid was obtained. In plasma and bronchoalveolar lavage fluid, levels of interleukin-6, interleukin-8, elastase-&agr;(1)-antitrypsin complexes, thrombin–antithrombin complexes, plasminogen activator activity, and plasminogen activator inhibitor-1 were determined by means of enzyme-linked immunosorbent assay. Main Results: In all patients, cardiac surgery was associated with systemic inflammation, evidenced by an increase in plasma levels of interleukin-6, interleukin-8, and elastase-&agr;(1)-antitrypsin complexes compared with presurgery levels (p < .001). Prior to onset of transfusion-related acute lung injury, systemic interleukin-8 and interleukin-6 levels were higher compared with nontransfused controls (p < .01). In transfusion-related acute lung injury cases, bronchoalveolar lavage fluid levels of interleukin-8, interleukin-6, and elastase-&agr;(1)-antitrypsin complexes were elevated compared with control groups (p < .05). Both plasma and bronchoalveolar lavage fluid levels of thrombin–antithrombin complexes were enhanced in transfusion-related acute lung injury cases compared with control groups (p < .01). Bronchoalveolar lavage fluid levels of plasminogen activator activity were decreased due to an increase in plasminogen activator inhibitor-1 levels in transfusion-related acute lung injury cases compared with control groups (p < .01), indicating suppressed fibrinolysis. Conclusions: Prior to onset of transfusion-related acute lung injury, there is systemic inflammation and neutrophil sequestration. Transfusion-related acute lung injury is characterized by both systemic and pulmonary inflammation and activation of neutrophils, as well as enhanced coagulation and suppressed fibrinolysis.

Mechanical ventilation with lower tidal volumes does not influence the prescription of opioids or sedatives

IntroductionWe compared the effects of mechanical ventilation with a lower tidal volume (VT) strategy versus those of greater VT in patients with or without acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) on the use of opioids and sedatives.MethodsThis is a secondary analysis of a previously conducted before/after intervention study, which consisting of feedback and education on lung protective mechanical ventilation using lower VT. We evaluated the effects of this intervention on medication prescriptions from days 0 to 28 after admission to our multidisciplinary intensive care unit.ResultsMedication prescriptions in 23 patients before and 38 patients after intervention were studied. Of these patients, 10 (44%) and 15 (40%) suffered from ALI/ARDS. The VT of ALI/ARDS patients declined from 9.7 ml/kg predicted body weight (PBW) before to 7.8 ml/kg PBW after the intervention (P = 0.007). For patients who did not have ALI/ARDS there was a trend toward a decline from 10.2 ml/kg PBW to 8.6 ml/kg PBW (P = 0.073). Arterial carbon dioxide tension was significantly greater after the intervention in ALI/ARDS patients. Neither the proportion of patients receiving opioids or sedatives, or prescriptions at individual time points differed between pre-intervention and post-intervention. Also, there were no statistically significant differences in doses of sedatives and opioids. Findings were no different between non-ALI/ARDS patients and ALI/ARDS patients.ConclusionConcerns regarding sedation requirements with use of lower VT are unfounded and should not preclude its use in patients with ALI/ARDS.

Tracheotomy does not affect reducing sedation requirements of patients in intensive care – a retrospective study

IntroductionTranslaryngeal intubated and ventilated patients often need sedation to treat anxiety, agitation and/or pain. Current opinion is that tracheotomy reduces sedation requirements. We determined sedation needs before and after tracheotomy of intubated and mechanically ventilated patients.MethodsWe performed a retrospective analysis of the use of morphine, midazolam and propofol in patients before and after tracheotomy.ResultsOf 1,788 patients admitted to our intensive care unit during the study period, 129 (7%) were tracheotomized. After the exclusion of patients who received a tracheotomy before or at the day of admittance, 117 patients were left for analysis. The daily dose (DD; the amount of sedatives for each day) divided by the mean daily dose (MDD; the mean amount of sedatives per day for the study period) in the week before and the week after tracheotomy was 1.07 ± 0.93 DD/MDD versus 0.30 ± 0.65 for morphine, 0.84 ± 1.03 versus 0.11 ± 0.46 for midazolam, and 0.62 ± 1.05 versus 0.15 ± 0.45 for propofol (p < 0.01). However, when we focused on a shorter time interval (two days before and after tracheotomy), there were no differences in prescribed doses of morphine and midazolam. Studying the course in DD/MDD from seven days before the placement of tracheotomy, we found a significant decline in dosage. From day -7 to day -1, morphine dosage (DD/MDD) declined by 3.34 (95% confidence interval -1.61 to -6.24), midazolam dosage by 2.95 (-1.49 to -5.29) and propofol dosage by 1.05 (-0.41 to -2.01). After tracheotomy, no further decrease in DD/MDD was observed and the dosage remained stable for all sedatives. Patients in the non-surgical and acute surgical groups received higher dosages of midazolam than patients in the elective surgical group. Time until tracheotomy did not influence sedation requirements. In addition, there was no significant difference in sedation between different patient groups.ConclusionIn our intensive care unit, sedation requirements were not further reduced after tracheotomy. Sedation requirements were already sharply declining before tracheotomy was performed.

Adaptive support ventilation with protocolized de-escalation and escalation does not accelerate tracheal extubation of patients after nonfast-track cardiothoracic surgery.

BACKGROUND:It is uncertain whether adaptive support ventilation (ASV) accelerates weaning of nonfast-track cardiothoracic surgery patients. A lower operator set %-minute ventilation with ASV may allow for an earlier definite switch from controlled to assisted ventilation, potentially hastening tracheal extubation. We hypothesized that ASV using protocolized de-escalation and escalation of operator set %-minute ventilation (ASV-DE) reduces time until tracheal extubation compared with ASV using a fixed operator set %-minute ventilation (standard ASV) in uncomplicated patients after nonfast-track coronary artery bypass graft. METHODS:We performed a randomized controlled trial comparing ASV-DE with standard ASV. With ASV-DE, as soon as body temperature was >35.0°C with pH >7.25, operator set %-minute ventilation was decreased stepwise to a minimum of 70%. RESULTS:Sixty-three patients were randomized to ASV-DE, and 63 patients to standard ASV. The duration of mechanical ventilation was not different between groups (10.8 [6.5–16.1] vs 10.7 [6.6–13.9] hours, ASV-DE versus standard ASV; P = 0.32). Time until the first assisted breathing period was shorter (3.1 [2.0–6.7] vs 3.9 [2.1–7.5] hours) and the number of assisted ventilation episodes was higher (78 [34–176] vs 57 [32–116] episodes), but differences did not reach statistical significance. The duration of assisted ventilation episodes that ended with tracheal extubation was different between groups (2.5 [0.9–4.6] vs 1.4 [0.3–3.5] hours, ASV-DE versus standard ASV; P < 0.05). CONCLUSION:Compared with standard ASV, weaning of patients after nonfast-track coronary artery bypass graft using ASV with protocolized de-escalation and escalation does not shorten time to tracheal extubation.

Determinants of Tidal Volumes with Adaptive Support Ventilation : A Multicenter Observational Study

INTRODUCTION:In the present study, we investigated the behavior of adaptive support ventilation (ASV) in patients after cardiothoracic surgery. We determined tidal volumes (Vt) and factors that influence Vt with this mode of microprocessor-controlled mechanical ventilation (MV). METHODS:This was a prospective, multicenter, observational study in three Dutch intensive care units over a 5-mo period. MV data were collected during steady-state after arrival in the intensive care unit. RESULTS:Data were collected for 346 consecutive patients after cardiothoracic surgery: 262 patients weaned with ASV, and 84 patients weaned with pressure-controlled/pressure-support MV. With ASV the mean (± sd) Vt expressed per kilogram actual body weight was 7.1 ± 1.6 mL. Expressed per kilogram ideal body weight (IBW), Vt was 8.3 ± 1.5 mL. In patients with a correctly set body weight (SBW) (i.e., the IBW), Vt was 8.1 ± 1.4 mL/kg. With pressure-controlled/pressure-support-MV Vt was 7.3 ± 1.4 mL/kg IBW (P < 0.001 vs ASV). Multivariate logistic regression analysis showed Vt with ASV to be dependent on only two parameters: respiratory rate and the correctness of SBW. CONCLUSIONS:Vt with ASV seems to be dependent on two parameters: respiratory rate and the correctness of SBW. The first factor is not clinically important because respiratory rate is automatically chosen by the microprocessor. The second factor is clinically important because it is the only factor that can be influenced by the operator. Our data show the importance of setting the correct weight with ASV. With ASV, Vt are >8 mL/kg IBW in a substantial number of patients. Randomized clinical trials should be performed to compare ASV with other ventilation modes.

Adaptive Support Ventilation May Deliver Unwanted Respiratory Rate–Tidal Volume Combinations in Patients with Acute Lung Injury Ventilated According to an Open Lung Concept

BACKGROUND With adaptive support ventilation, respiratory rate and tidal volume (V(T)) are a function of the Otis least work of breathing formula. We hypothesized that adaptive support ventilation in an open lung ventilator strategy would deliver higher V(T)s to patients with acute lung injury. METHODS Patients with acute lung injury were ventilated according to a local guideline advising the use of lower V(T) (6-8 ml/kg predicted body weight), high concentrations of positive end-expiratory pressure, and recruitment maneuvers. Ventilation parameters were recorded when the ventilator was switched to adaptive support ventilation, and after recruitment maneuvers. If V(T) increased more than 8 ml/kg predicted body weight, airway pressure was limited to correct for the rise of V(T). RESULTS Ten patients with a mean (±SD) Pao(2)/Fio(2) of 171 ± 86 mmHg were included. After a switch from pressure-controlled ventilation to adaptive support ventilation, respiratory rate declined (from 31 ± 5 to 21 ± 6 breaths/min; difference = 10 breaths/min, 95% CI 3-17 breaths/min, P = 0.008) and V(T) increased (from 6.5 ± 0.8 to 9.0 ± 1.6 ml/kg predicted body weight; difference = 2.5 ml, 95% CI 0.4-4.6 ml/kg predicted body weight, P = 0.02). Pressure limitation corrected for the rise of V(T), but minute ventilation declined, forcing the user to switch back to pressure-controlled ventilation. CONCLUSIONS Adaptive support ventilation, compared with pressure-controlled ventilation in an open lung strategy setting, delivers a lower respiratory rate-higher V(T) combination. Pressure limitation does correct for the rise of V(T), but leads to a decline in minute ventilation.

Laser speckle contrast imaging identifies ischemic areas on gastric tube reconstructions following esophagectomy

AbstractGastric tube reconstruction (GTR) is a high-risk surgical procedure with substantial perioperative morbidity. Compromised arterial blood supply and venous congestion are believed to be the main etiologic factors associated with early and late anastomotic complications. Identifying low blood perfusion areas may provide information on the risks of future anastomotic leakage and could be essential for improving surgical techniques. The aim of this study was to generate a method for gastric microvascular perfusion analysis using laser speckle contrast imaging (LSCI) and to test the hypothesis that LSCI is able to identify ischemic regions on GTRs.Patients requiring elective laparoscopy-assisted GTR participated in this single-center observational investigation. A method for intraoperative evaluation of blood perfusion and postoperative analysis was generated and validated for reproducibility. Laser speckle measurements were performed at 3 different time pointes, baseline (devascularized) stomach (T0), after GTR (T1), and GTR at 20° reverse Trendelenburg (T2).Blood perfusion analysis inter-rater reliability was high, with intraclass correlation coefficients for each time point approximating 1 (P < 0.0001). Baseline (T0) and GTR (T1) mean blood perfusion profiles were highest at the base of the stomach and then progressively declined towards significant ischemia at the most cranial point or anastomotic tip (P < 0.01). After GTR, a statistically significant improvement in mean blood perfusion was observed in the cranial gastric regions of interest (P < 0.05). A generalized significant decrease in mean blood perfusion was observed across all GTR regions of interest during 20° reverse Trendelenburg (P < 0.05).It was feasible to implement LSCI intraoperatively to produce blood perfusion assessments on intact and reconstructed whole stomachs. The analytical design presented in this study resulted in good reproducibility of gastric perfusion measurements between different investigators. LSCI provides spatial and temporal information on the location of adequate tissue perfusion and may thus be an important aid in optimizing surgical and anesthesiological procedures for strategically selecting anastomotic site in patients undergoing esophagectomy with GTR.