Differential effects of speed and volume on transfusion-associated circulatory overload: A randomized study in rats.

BACKGROUND AND OBJECTIVES: Transfusion-associated circulatory overload (TACO) is the primary cause of transfusion-related mortality. Speed and volume of transfusion are major risk factors. The aim of this study was to investigate the interaction of red blood cell (RBC) transfusion speed and volume on the development of TACO. MATERIALS AND METHODS: A validated model for TACO in anaemic Lewis rats with an acute myocardial infarction was used. The effect on pulmonary hydrostatic pressure of one, two or four units of packed RBCs transfused in either 30 or 60 min was evaluated (3.3-26.6 ml·kg-1 ·hr-1 ). Pulmonary capillary pressure was measured as left ventricular end-diastolic pressure (LVEDP). Cardiac stress biomarkers atrial natriuretic-peptide (ANP) and N-terminal pro-brain natriuretic peptide (NT-proBNP) were measured 1-h post-transfusion. RESULTS: Thirty animals were included (n = 5 per group). Transfusion of RBCs increased LVEDP in a volume-dependent manner (ΔLVEDP [mmHg]: -0.95, +0.50, +6.26, p < 0.001). Fast transfusion increased overall ΔLVEDP by +3.5 mmHg and up to +11.8 mmHg in the four units' group (p = 0.016). Doubling transfusion speed increased ΔLVEDP more than doubling volume in the larger volume groups. No difference in ANP or NT-proBNP were seen in high transfusion volume or groups. CONCLUSION: Transfusion volume dose-dependently increased LVEDP, with speed of transfusion rapidly elevating LVEDP at higher transfusion volumes. ANP and NT-proBNP were not impacted by transfusion volume or speed in this model. TACO is seen as purely volume overload, however, this study emphasizes that limiting transfusion speed, as a modifiable risk factor, might aid in preventing TACO.

Volume incompliance and transfusion are essential for transfusion-associated circulatory overload: a novel animal model.

BACKGROUND: Transfusion-associated circulatory overload (TACO) is the predominant complication of transfusion resulting in death. The pathophysiology is poorly understood, but inability to manage volume is associated with TACO, and observational data suggest it is different from simple cardiac overload due to fluids. We developed a two-hit TACO animal model to assess the role of volume incompliance ("first-hit") and studied whether volume overload ("second-hit") by red blood cell (RBC) transfusion is different compared to fluids (Ringer's lactate [RL]). MATERIALS AND METHODS: Male adult Lewis rats were stratified into a control group (no intervention) or a first hit: either myocardial infarction (MI) or acute kidney injury (AKI). Animals were randomized to a second hit of either RBC transfusion or an equal volume of RL. A clinically relevant difference was defined as an increase in left ventricular end-diastolic pressure (ΔLVEDP) of +4.0 mm Hg between the RBC and RL groups. RESULTS: In control animals (without first hit) LVEDP was not different between infusion groups (Δ + 1.6 mm Hg). LVEDP increased significantly more after RBCs compared to RL in animals with MI (Δ7.4 mm Hg) and AKI (Δ + 5.4 mm Hg), respectively. Volume-incompliant rats matched clinical TACO criteria in 92% of transfused versus 25% of RL-infused animals, with a greater increase in heart rate and significantly higher blood pressure. CONCLUSION: To our knowledge, this is the first animal model for TACO, showing that a combination of volume incompliance and transfusion is essential for development of circulatory overload. This model allows for further testing of mechanistic factors as well as therapeutic approaches.

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.

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.

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.

Effect of transfusion of fresh frozen plasma on parameters of endothelial condition and inflammatory status in non-bleeding critically ill patients: a prospective substudy of a randomized trial.

INTRODUCTION: Much controversy exists on the effect of a fresh frozen plasma (FFP) transfusion on systemic inflammation and endothelial damage. Adverse effects of FFP have been well described, including acute lung injury. However, it is also suggested that a higher amount of FFP decreases mortality in trauma patients requiring a massive transfusion. Furthermore, FFP has an endothelial stabilizing effect in experimental models. We investigated the effect of fresh frozen plasma transfusion on systemic inflammation and endothelial condition. METHODS: A prospective predefined substudy of a randomized trial in coagulopathic non-bleeding critically ill patients receiving a prophylactic transfusion of FFP (12 ml/kg) prior to an invasive procedure. Levels of inflammatory cytokines and markers of endothelial condition were measured in paired samples of 33 patients before and after transfusion. The statistical tests used were paired t test or the Wilcoxon signed-rank test. RESULTS: At baseline, systemic cytokine levels were mildly elevated in critically ill patients. FFP transfusion resulted in a decrease of levels of TNF-α (from 11.3 to 2.3 pg/ml, P = 0.01). Other cytokines were not affected. FFP also resulted in a decrease in systemic syndecan-1 levels (from 675 to 565 pg/ml, P = 0.01) and a decrease in factor VIII levels (from 246 to 246%, P <0.01), suggestive of an improved endothelial condition. This was associated with an increase in ADAMTS13 levels (from 24 to 32%, P <0.01) and a concomitant decrease in von Willebrand factor (vWF) levels (from 474 to 423%, P <0.01). CONCLUSIONS: A fixed dose of FFP transfusion in critically ill patients decreases syndecan-1 and factor VIII levels, suggesting a stabilized endothelial condition, possibly by increasing ADAMTS13, which is capable of cleaving vWF. TRIAL REGISTRATIONS: Trialregister.nl NTR2262, registered 26 March 2010 and Clinicaltrials.gov NCT01143909, registered 14 June 2010.

Methylprednisolone fails to attenuate lung injury in a mouse model of transfusion related acute lung injury.

BACKGROUND: Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion-related morbidity and mortality. Anecdotally, TRALI patients have been treated with corticosteroids. However, evidence for its therapeutic rationale in TRALI is lacking. We determined the effects of corticosteroids on lung injury in a "two-hit" mouse model of antibody-mediated TRALI. STUDY DESIGN AND METHODS: BALB/c mice were primed with lipopolysaccharide, after which TRALI was induced by injecting major histocompatibility complex (MHC)-I antibody against H2K(d) . Mice infused with phosphate-buffered saline served as controls. Simultaneously, one group of TRALI mice was infused with methylprednisolone (MPS; 2 mg/kg). Mice were supported by mechanical ventilation for 2 hours, after which bronchoalveolar lavage fluid (BALF) and lung homogenate were obtained. Statistics were obtained by one-way analysis of variance or Kruskal-Wallis. RESULTS: Injection of MHC-I antibodies resulted in TRALI, indicated by pulmonary edema and increased BALF levels of protein and the proinflammatory mediators macrophage inflammatory protein-2, keratinocyte-derived chemokine, and interleukin (IL)-6. Administration of MPS did not affect the amount of edema nor pulmonary protein and chemokine levels. MPS reduced systemic inflammatory reaction as well as IL-6 levels in the BALF. CONCLUSION: In a two-hit model of antibody-mediated TRALI, MPS attenuated the IL-6 host response, but failed to prevent the development of lung injury.

Utility of thromboelastography and/or thromboelastometry in adults with sepsis: a systematic review.

INTRODUCTION: Coagulation abnormalities are frequent in sepsis. Conventional coagulation assays, however, have several limitations. A surge of interest exists in the use of point-of-care tests to diagnose hypo- and hypercoagulability in sepsis. METHODS: MEDLINE, EMBASE, and the Cochrane Library were searched from 1 January 1980 to 31 December 2012. The search was limited to adults, and language was limited to English. Reference lists of retrieved articles were hand-searched for additional studies. Ongoing trials were searched on http://www.controlled-trials.com and http://www.clinicaltrials.gov. Studies addressing TEG/ROTEM measurements in adult patients with sepsis admitted to the ICU were considered eligible. RESULTS: Of 680 screened articles, 18 studies were included, of which two were randomized controlled trials, and 16 were observational cohort studies. In patients with sepsis, results show both hyper- and hypocoagulability, as well as TEG/ROTEM values that fell within reference values. Both hyper- and hypocoagulability were to some extent associated with diffuse intravascular coagulation. Compared with conventional coagulation tests, TEG/ROTEM can detect impaired fibrinolysis, which can possibly help to discriminate between sepsis and systemic inflammatory response syndrome (SIRS). A hypocoagulable profile is associated with increased mortality. The value of TEG/ROTEM to identify patients with sepsis who could possibly benefit from therapies interfering with the coagulation system could not be assessed, because studies addressing this topic were limited. CONCLUSION: TEG/ROTEM could be a promising tool in diagnosing alterations in coagulation in sepsis. Further research on the value of TEG/ROTEM in these patients is warranted. Given that coagulopathy is a dynamic process, sequential measurements are needed to understand the coagulation patterns in sepsis, as can be detected by TEG/ROTEM.

Cardiac arrest patients have an impaired immune response, which is not influenced by induced hypothermia.

INTRODUCTION: Induced hypothermia is increasingly applied as a therapeutic intervention in ICUs. One of the underlying mechanisms of the beneficial effects of hypothermia is proposed to be reduction of the inflammatory response. However, a fear of reducing the inflammatory response is an increased infection risk. Therefore, we studied the effect of induced hypothermia on immune response after cardiac arrest. METHODS: A prospective observational cohort study in a mixed surgical-medical ICU. Patients admitted at the ICU after surviving cardiac arrest were included and during 24 hours body temperature was strictly regulated at 33°C or 36°C. Blood was drawn at three time points: after reaching target temperature, at the end of the target temperature protocol and after rewarming to 37°C. Plasma cytokine levels and response of blood leucocytes to stimulation with toll-like receptor (TLR) ligands lipopolysaccharide (LPS) from Gram-negative bacteria and lipoteicoic acid (LTA) from Gram-positive bacteria were measured. Also, monocyte HLA-DR expression was determined. RESULTS: In total, 20 patients were enrolled in the study. Compared to healthy controls, cardiac arrest patients kept at 36°C (n = 9) had increased plasma cytokines levels, which was not apparent in patients kept at 33°C (n = 11). Immune response to TLR ligands in patients after cardiac arrest was generally reduced and associated with lower HLA-DR expression. Patients kept at 33°C had preserved ability of immune cells to respond to LPS and LTA compared to patients kept at 36°C. These differences disappeared over time. HLA-DR expression did not differ between 33°C and 36°C. CONCLUSIONS: Patients after cardiac arrest have a modest systemic inflammatory response compared to healthy controls, associated with lower HLA-DR expression and attenuated immune response to Gram-negative and Gram-positive antigens, the latter indicative of an impaired immune response to bacteria. Patients with a body temperature of 33°C did not differ from patients with a body temperature of 36°C, suggesting induced hypothermia does not affect immune response in patients with cardiac arrest. TRIAL REGISTRATION: ClinicalTrials.gov NCT01020916, registered 25 November 2009.

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.

Induced hypothermia is protective in a rat model of pneumococcal pneumonia associated with increased adenosine triphosphate availability and turnover*.

OBJECTIVE: To determine the effect of induced hypothermia on bacterial growth, lung injury, and mitochondrial function in a rat model of pneumococcal pneumosepsis. DESIGN: Animal study. SETTING: University research laboratory. SUBJECTS: Male Sprague-Dawley rats. INTERVENTIONS: Subjects were inoculated intratracheally with Streptococcus pneumoniae and controls received saline. After the development of pneumonia, mechanical ventilation was started with or without induced mild hypothermia (32 °C). Bacterial growth and inflammatory markers were determined in bronchoalveolar lavage fluid, blood, and organs. Oxidative phosphorylation and adenosine triphosphate contents were measured in mitochondria isolated from the liver and soleus muscle. MEASUREMENTS AND MAIN RESULTS: Inoculation with S. pneumoniae resulted in severe pneumonia with bacterial dissemination, distal organ injury, and blunted peripheral oxygen consumption on mechanical ventilation. Hypothermia did not affect bacterial growth in bronchoalveolar lavage fluid and in homogenized lungs compared with normothermic controls but was associated with reduced bacterial dissemination to the spleen with a trend toward reduced bacterial load in blood and liver. Hypothermia reduced lung injury, exemplified by reductions in pulmonary cell influx and bronchoalveolar lavage fluid protein levels compared with controls. Hypothermia reduced bronchoalveolar lavage fluid levels of interleukin-1ß, tended to reduce bronchoalveolar lavage fluid CINC-3 levels, but no effect was observed on bronchoalveolar lavage fluid tumor necrosis factor-α and interleukin-6 levels. Induced hypothermia restored the fall in oxygen consumption and adenosine triphosphate levels in the liver, whereas adenosine triphosphate/adenosine diphosphate ratios remained low. In muscle, induced hypothermia also reversed low oxygen consumption as a result of pneumonia, but with an increase in adenosine triphosphate levels, whereas adenosine triphosphate/adenosine diphosphate ratios were low. CONCLUSION: Hypothermia did not adversely affect bacterial growth, but rather reduced bacterial dissemination in a rat model of pneumococcal pneumosepsis. Furthermore, hypothermia reduced lung injury associated with restored adenosine triphosphate availability and turnover. These findings suggest that hypothermia may reduce organ injury by preventing sepsis-related mitochondrial dysfunction.

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-α1-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-α1-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-α1-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.

The effect of blood transfusion on pulmonary permeability in cardiac surgery patients: a prospective multicenter cohort study.

BACKGROUND: There is an association between blood transfusion and pulmonary complications in cardiac surgery. Mediators of increased pulmonary vascular leakage after transfusion are unknown. We hypothesized that factors may include antibodies or bioactive lipids, which have been implicated in transfusion-related acute lung injury. STUDY DESIGN AND METHODS: We performed a prospective cohort study in two university hospital intensive care units in the Netherlands. Pulmonary vascular permeability was measured in cardiac surgery patients after receiving no, restrictive (one or two transfusions), or multiple (five or more transfusions) transfusions (n=20 per group). The pulmonary leak index (PLI), using (67) Ga-labeled transferrin, was determined within 3 hours postoperatively. Blood products were screened for bioactive lipid accumulation and the presence of antibodies. RESULTS: The PLI was elevated in all groups after cardiac surgery. Transfused patients had a higher PLI compared to nontransfused patients (33×10(-3) ± 20×10(-3) vs. 23×10(-3) ± 11×10(-3)/min, p<0.01). The amount of red blood cell (RBC) products, but not of fresh-frozen plasma or platelets, was associated with an increase in PLI (ß, 1.6 [0.2-3.0]). Concerning causative factors in the blood product, neither the level of bioactive lipids nor the presence of antibodies was associated with an increase in PLI. Patient factors such as surgery risk and time on cardiopulmonary bypass did not influence the risk of pulmonary leakage after blood transfusion. CONCLUSIONS: Transfusion in cardiothoracic surgery patients is associated with an increase in pulmonary capillary permeability, an effect that was dose dependent for RBC products. The level of bioactive lipids or the presence of HLA or HNA antibodies in the transfused products were not associated with increased pulmonary capillary permeability.

Benefits and risks of manual hyperinflation in intubated and mechanically ventilated intensive care unit patients: a systematic review.

INTRODUCTION: Manual hyperinflation (MH), a frequently applied maneuver in critically ill intubated and mechanically ventilated patients, is suggested to mimic a cough so that airway secretions are mobilized toward the larger airways, where they can easily be removed. As such, MH could prevent plugging of the airways. METHODS: We performed a search in the databases of Medline, Embase, and the Cochrane Library from January 1990 to April 2012. We systematically reviewed the literature on evidence for postulated benefits and risks of MH in critically ill intubated and mechanically ventilated patients. RESULTS: The search identified 50 articles, of which 19 were considered relevant. We included 13 interventional studies and six observational studies. The number of studies evaluating physiological effects of MH is limited. Trials differed too much to permit meta-analysis. It is uncertain whether MH was applied similarly in the retrieved studies. Finally, most studies are underpowered to show clinical benefit of MH. Use of MH is associated with short-term improvements in lung compliance, oxygenation, and secretion clearance, without changes in outcomes. MH has been reported to be associated with short-term and probably clinically insignificant side effects, including decreases in cardiac output, alterations of heart rates, and increased central venous pressures. CONCLUSIONS: Studies have failed to show that MH benefits critically ill intubated and mechanically ventilated patients. MH is infrequently associated with short-term side effects.

Prophylactic furosemide to prevent transfusion-associated circulatory overload: a randomized controlled study in rats.

Transfusion-associated circulatory overload (TACO) is the leading cause of transfusion related morbidity and mortality. The only treatment is empirical use of furosemide. Our aim was to investigate if furosemide can prevent TACO. A randomized controlled trial was performed using a previously validated two-hit rat model for TACO. Volume incompliance was induced (first hit) in anemic, anesthetized Lewis rats. Rats were randomized to placebo, low-dose (5 mg kg-1) or high-dose (15 mg kg-1) furosemide-administered prior to transfusion (second-hit) and divided over two doses. Primary outcome was change in left-ventricular end-diastolic pressure (∆LVEDP) pre- compared to post-transfusion. Secondary outcomes included changes in preload, afterload, contractility and systemic vascular resistance, as well as pulmonary outcomes. Furosemide treated animals had a significantly lower ∆LVEDP compared to placebo (p = 0.041), a dose-response effect was observed. ∆LVEDP in placebo was median + 8.7 mmHg (IQR 5.9-11), + 3.9 (2.8-5.6) in the low-dose and 1.9 (- 0.6 to 5.6) in the high-dose group. The effect of furosemide became apparent after 15 min. While urine output was significantly higher in furosemide treated animals (p = 0.03), there were no significant changes in preload, afterload, contractility or systemic vascular resistance. Furosemide rapidly and dose-dependently decreases the rise in hydrostatic pulmonary pressure following transfusion, essential for preventing TACO.

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.

On-ward participation of a hospital pharmacist in a Dutch intensive care unit reduces prescribing errors and related patient harm: an intervention study.

INTRODUCTION: Patients admitted to an intensive care unit (ICU) are at high risk for prescribing errors and related adverse drug events (ADEs). An effective intervention to decrease this risk, based on studies conducted mainly in North America, is on-ward participation of a clinical pharmacist in an ICU team. As the Dutch Healthcare System is organized differently and the on-ward role of hospital pharmacists in Dutch ICU teams is not well established, we conducted an intervention study to investigate whether participation of a hospital pharmacist can also be an effective approach in reducing prescribing errors and related patient harm (preventable ADEs) in this specific setting. METHODS: A prospective study compared a baseline period with an intervention period. During the intervention period, an ICU hospital pharmacist reviewed medication orders for patients admitted to the ICU, noted issues related to prescribing, formulated recommendations and discussed those during patient review meetings with the attending ICU physicians. Prescribing issues were scored as prescribing errors when consensus was reached between the ICU hospital pharmacist and ICU physicians. RESULTS: During the 8.5-month study period, medication orders for 1,173 patients were reviewed. The ICU hospital pharmacist made a total of 659 recommendations. During the intervention period, the rate of consensus between the ICU hospital pharmacist and ICU physicians was 74%. The incidence of prescribing errors during the intervention period was significantly lower than during the baseline period: 62.5 per 1,000 monitored patient-days versus 190.5 per 1,000 monitored patient-days, respectively (P < 0.001). Preventable ADEs (patient harm, National Coordinating Council for Medication Error Reporting and Prevention severity categories E and F) were reduced from 4.0 per 1,000 monitored patient-days during the baseline period to 1.0 per 1,000 monitored patient-days during the intervention period (P = 0.25). Per monitored patient-day, the intervention itself cost €3, but might have saved €26 to €40 by preventing ADEs. CONCLUSIONS: On-ward participation of a hospital pharmacist in a Dutch ICU was associated with significant reductions in prescribing errors and related patient harm (preventable ADEs) at acceptable costs per monitored patient-day. TRIAL REGISTRATION NUMBER: ISRCTN92487665.

Review of a large clinical series: the value of routinely obtained chest radiographs on admission to a mixed medical--surgical intensive care unit.

BACKGROUND AND OBJECTIVES: The efficacy of routinely obtained chest radiographs (CXRs) on admission to the intensive care unit (ICU) is largely unknown. The current study investigated the efficacy of routinely obtained admission CXRs and determined whether the value of this diagnostic test was dependent on patient category. MATERIALS AND METHODS: Prospective nonrandomized controlled study. including 1081 admission CXRs of 1330 patients admitted to a 28-bed mixed medical-surgical university-affiliated ICU, over a 10-month period. To determine the value of admission CXRs, 2 categories of efficacy were used: diagnostic efficacy (the number of CXRs with a new or progressive major finding divided by the total number of CXRs) and therapeutic efficacy (the number of CXRs resulting in a change in clinical management divided by the total number of CXRs). Efficacy <15% was considered low. Patients were subclassified into subcategories on the basis of type of admission. RESULTS: Of all admission CXRs, 227 were clinically indicated and 854 were routinely obtained to establish a baseline prior to admission to ICU. Diagnostic efficacy of routinely obtained admission CXRs was 11%. The majority of abnormalities were malposition of invasive devices and severe pulmonary congestion. Therapeutic efficacy of routinely obtained admission CXRs was only 5%. Subgroup analysis showed highest efficacy in nonsurgical patients. CONCLUSIONS: In our mixed medical-surgical ICU the diagnostic and therapeutic efficacy of routinely obtained admission CXRs is low, though not completely negligible. Highest efficacy of CXRs was found in nonsurgical patients. Prospective studies are needed to determine whether abolishing this diagnostic test is a safe strategy.

Performance of manual hyperinflation: a skills lab study among trained intensive care unit nurses.

BACKGROUND: The aim of manual hyperinflation (MH) is to mobilize airway secretions and prevent sputum plugging in intubated and mechanically ventilated patients. With MH, the nurse applies a larger than normal breath with a slow inspiratory flow and, after an inspiratory pause, a high expiratory flow is created by completely releasing the resuscitation bag. MATERIAL/METHODS: This was a prospective observational study in a skills lab of a university hospital. Intensive care unit nurses performed MH procedures for an imaginary patient in three different compliance settings. Data were collected via direct video recordings and an air-flow analyzer. RESULTS: One hundred nurses participated. Video recordings demonstrated inappropriate performance of MH, reflected by the appearance of inspirations which were too rapid (53% of cases), absence of holds (60%), and absence of complete release of the resuscitation bag (78%). In the majority of cases the applied volumes were too large according to what was advised in the local guideline (80%). Peak inspiratory flow was 70 (range: 55-89) l/min for all compliance settings and peak expiratory flows were low: for over-compliant (46, range: 42-51), normal (51, range: 45-57), and noncompliant lungs (58, range: 52-64 l/min). CONCLUSIONS: Performance of MH by certified ICU nurses is far from appropriate. These results emphasize the necessity for clearer guidelines with explicit directions for this frequently applied procedure, if it is decided to practice it in the daily care of intubated and mechanically ventilated patients.

Decision making in interhospital transport of critically ill patients: national questionnaire survey among critical care physicians.

OBJECTIVE: This study assessed the relative importance of clinical and transport-related factors in physicians' decision-making regarding the interhospital transport of critically ill patients. METHODS: The medical heads of all 95 ICUs in The Netherlands were surveyed with a questionnaire using 16 case vignettes to evaluate preferences for transportability; 78 physicians (82%) participated. The vignettes varied in eight factors with regard to severity of illness and transport conditions. Their relative weights were calculated for each level of the factors by conjoint analysis and expressed in beta. The reference value (beta = 0) was defined as the optimal conditions for critical care transport; a negative beta indicated preference against transportability. RESULTS: The type of escorting personnel (paramedic only: beta = -3.1) and transport facilities (standard ambulance beta = -1.21) had the greatest negative effect on preference for transportability. Determinants reflecting severity of illness were of relative minor importance (dose of noradrenaline beta = -0.6, arterial oxygenation beta = -0.8, level of peep beta = -0.6). Age, cardiac arrhythmia, and the indication for transport had no significant effect. CONCLUSIONS: Escorting personnel and transport facilities in interhospital transport were considered as most important by intensive care physicians in determining transportability. When these factors are optimal, even severely critically ill patients are considered able to undergo transport. Further clinical research should tailor transport conditions to optimize the use of expensive resources in those inevitable road trips.