Sjoerd Greuters

Acute and delayed mild coagulopathy are related to outcome in patients with isolated traumatic brain injury

IntroductionThe relationship between isolated traumatic brain injury (TBI) associated coagulopathy and patient prognosis frequently lacks information regarding the time course of coagulation disorders throughout the post-traumatic period. This study was conducted to assess the prevalence and time course of post-traumatic coagulopathy in patients with isolated TBI and the relationship of these hemostatic disorders with outcome.MethodsThe local Human Subjects Committee approved the study. We retrospectively studied the medical records of computed tomography (CT)-confirmed isolated TBI patients with an extracranial abbreviated injury scale (AIS) <3 who were primarily referred to a Level 1 trauma centre in Amsterdam (n = 107). Hemostatic parameters including activated partial thromboplastin time (aPTT), prothrombin time (PT), platelet count, hemoglobin, hematocrit, glucose, pH and lactate levels were recorded throughout a 72-hour period as part of a routine standardized follow-up of TBI. Coagulopathy was defined as a aPPT >40 seconds and/or a PTT in International Normalized Ratio (INR) >1.2 and/or a platelet count <120*109/l.ResultsPatients were mostly male, aged 48 ± 20 years with a median injury severity score of 25 (range 20 to 25). Early coagulopathy as diagnosed in the emergency department (ED) occurred in 24% of all patients. The occurrence of TBI-related coagulopathy increased to 54% in the first 24 hours post-trauma. In addition to an increased age and disturbed pupillary reflex, both coagulopathy upon ED arrival and during the first 24 hours post-trauma provided an independent prognostic factor for unfavorable outcome (odds ratio (OR) 3.75 (95% CI 1.07 to 12.51; P = 0.04) and OR 11.61 (2.79 to 48.34); P = 0.003).ConclusionsOur study confirms a high prevalence of early and delayed coagulopathy in patients with isolated TBI, which is strongly associated with an unfavorable outcome. These data support close monitoring of hemostasis after TBI and indicate that correction of coagulation disturbances might need to be considered.

Prehospital endotracheal intubation in patients with severe traumatic brain injury: Guidelines versus reality

The international Brain Trauma Foundation guidelines recommend prehospital endotracheal intubation in all patients with traumatic brain injury (TBI) and a Glasgow Coma Scale (GCS)< or =8. Close adherence to these guidelines is associated with improved outcome, but not all severely injured TBI patients receive adequate prehospital airway support. Here we hypothesized that guideline adherence varies when skills are involved that rely on training and expertise, such as endotracheal intubation. We retrospectively studied the medical records of CT-confirmed TBI patients with a GCS< or =8 who were referred to a level 1 trauma centre in Amsterdam (n=127). Records were analyzed for demographic parameters, prehospital treatment modalities, involvement of an emergency medical service (EMS) and respiratory and metabolic parameters upon arrival at the hospital. Patients were mostly male, aged 45+/-21 years with a median injury severity score (ISS) of 26. Of all patients for whom guidelines recommend endotracheal intubation, only 56% were intubated. In 21 out of 106 severe cases an EMS was not called for, suggesting low guideline adherence. Especially those TBI patients treated by paramedics tended to develop higher levels of stress markers like glucose and lactate. We observed a low degree of adherence to intubation guidelines in a Dutch urban area. Main reasons for low adherence were the unavailability of specialized care, scoop and run strategies and absence of a specialist physician in cases where intubation was recommended. The discrepancy between guidelines and reality warrants changing practice to improve guideline compliance and optimize outcome in TBI patients.

Hyperfibrinolysis in out of hospital cardiac arrest is associated with markers of hypoperfusion

AIM OF THE STUDY This study investigated the incidence of hyperfibrinolysis upon emergency department (ED) admission in patients with out of hospital cardiac arrest (OHCA), and the association of the degree of hyperfibrinolysis with markers of hypoperfusion. METHODS From 30 OHCA patients, cardiopulmonary resuscitation (CPR) time, pH, base excess (BE), and serum lactate were measured upon ED admission. A 20% decrease of rotational thromboelastometry maximum clot firmness (MCF) was defined as hyperfibrinolysis. Lysis parameters included maximum lysis (ML), lysis onset time (LOT) and lysis index at 30 and 45 min (LI30/LI45). The study was approved by the Human Subjects Committee. RESULTS Hyperfibrinolysis was present in 53% of patients. Patients with hyperfibrinolysis had longer median CPR times (36 (15-55) vs. 10 (7-18)min; P=0.001), a prolonged activated partial thromboplastin time (54 ± 16 vs. 38 ± 10s; P=0.006) and elevated D-dimers (6.1 ± 2.1 vs. 2.3 ± 2.0 μg/ml; P=0.02) when compared to patients without hyperfibrinolysis. Hypoperfusion markers, including pH (6.96 ± 0.11 vs. 7.17 ± 0.15; P<0.001), base excess (-20.01 ± 3.53 vs. -11.91 ± 6.44; P<0.001) and lactate (13.1 ± 3.7 vs. 8.0 ± 3.7 mmol/l) were more disturbed in patients with hyperfibrinolysis than in non-hyperfibrinolytic subjects, respectively. The LOT showed a good association with CPR time (r=-0.76; P=0.003) and lactate (r=-0.68; P=0.01), and was longer in survivors (3222 ± 34s) than in non-survivors (1,356 ± 833; P=0.044). CONCLUSION A substantial part of OHCA patients develop hyperfibrinolysis in association with markers for hypoperfusion. Our data further suggest that the time to the onset of clot lysis may be an important marker for the severity of hyperfibrinolysis and patient outcome.

Effect of Secondary Prehospital Risk Factors on Outcome in Severe Traumatic Brain Injury in the Context of Fast Access to Trauma Care

BACKGROUND Prevention of secondary prehospital risk factors such as hypoxia and hypotension is likely to improve patient prognosis in severe traumatic brain injury (TBI). Because the Dutch trauma care organization is characterized by fast access to specialized trauma care due to the geographical situation, we investigated whether and to what extend secondary risk factors, such as hypoxia and hypotension, and measures, such as endotracheal intubation, affect outcome in severe TBI in the context of a region with fast access to trauma care. METHODS The medical records of 339 subsequent computed tomography-confirmed patients with TBI with a Glasgow coma scale (GCS) score≤8 who were primarily referred to a Level I trauma center in Amsterdam or Nijmegen in the Netherlands were retrospectively analyzed. RESULTS Multinomial logistic regression revealed that the strongest outcome predictors in our population were a disturbed pupillary reflex (odds ratio [OR], 5.8), a GCS score of 3 (OR, 4.9), and arterial hypotension (OR, 3.5). Interestingly, we observed no differences between intubated and nonintubated patients with respect to metabolic and respiratory parameters or mortality whereby the injury severity score was slightly higher in endotracheally intubated patients (32 [25-41]) versus nonintubated patients (25 [22-29]). CONCLUSION In agreement with others, GCS, a disturbed pupil reflex, and arterial hypotension were predictive for the prognosis of primarily referred patients with severe TBI in the Netherlands. In contrast, in the perspective of slightly higher injury scores in intubated patients, prehospital endotracheal intubation was not predictive for patient outcome.

Profound Effects of Cardiopulmonary Bypass Priming Solutions on the Fibrin Part of Clot Formation: An Ex Vivo Evaluation Using Rotation Thromboelastometry

OBJECTIVES Dilutional coagulopathy as a consequence of cardiopulmonary bypass (CPB) system priming may also be affected by the composition of the priming solution. The direct effects of distinct priming solutions on fibrinogen, one of the foremost limiting factors during dilutional coagulopathy, have been minimally evaluated. Therefore, the authors investigated whether hemodilution with different priming solutions distinctly affects the fibrinogen-mediated step in whole blood clot formation. DESIGN Prospective observational laboratory study. SETTING University hospital laboratory. PARTICIPANTS Eight male healthy volunteers. INTERVENTIONS Blood samples diluted with gelatin-, albumin-, or hydroxyethyl starch (HES)-based priming solutions were ex-vivo evaluated for clot formation by rotational thromboelastometry. MEASUREMENTS AND MAIN RESULTS The intrinsic pathway (INTEM) coagulation time increased from 186 +/- 19 seconds to 205 +/- 16, 220 +/- 17, and 223 +/- 18 seconds after dilution with gelatin-, albumin-, or HES-containing prime solutions (all p < 0.05 v baseline). The extrinsic pathway (EXTEM) coagulation time was only minimally affected by hemodilution. Moreover, all 3 priming solutions significantly reduced the INTEM and EXTEM maximum clot firmness. The HES-containing priming solution induced the largest decrease in the maximum clot firmness attributed to fibrinogen, from 13 +/- 1 mm (baseline) to 6 +/- 1 mm (p < 0.01 v baseline). CONCLUSIONS All studied priming solutions prolonged coagulation time and decreased clot formation, but the fibrinogen-limiting effect was the most profound for the HES-containing priming solution. These results suggest that the composition of priming solutions may distinctly affect blood clot formation, in particular with respect to the fibrinogen component in hemostasis.

Haemostatic and cranial computed tomography characteristics in patients with acute and delayed coagulopathy after isolated traumatic brain injury

Primary objective: To investigate whether the development of coagulopathy at different stages after isolated traumatic brain injury (TBI) is associated with distinct cranial computed tomography characteristics. Research design: Retrospective cohort study in 226 patients with moderate-to-severe isolated TBI who were categorized as subjects without coagulopathy or with acute temporary, acute sustained or delayed coagulopathy. Methods and procedures: Coagulopathy was defined as an activated partial thromboplastin time >40 seconds and/or prothrombin time (PT) >1.2 and/or platelet count <120*109 l−1. Cranial CT scans were assigned to the six-point Traumatic Coma Data Bank (TCDB) CT-classification. Main outcomes and results: Coagulopathy occurred in 44% of patients in the first 24-hours post-trauma. Patients with acute, sustained coagulopathy showed a prolonged PT (1.64 ± 0.89) when compared to patients without (1.03 ± 0.07), acute temporary (1.27 ± 0.22) or delayed coagulopathy (1.08 ± 0.06; p < 0.05). Patients with acute temporary or delayed coagulopathy had the worst TCDB CT classification scores, while mortality rates were the highest in patients with sustained or delayed coagulopathy. Conclusions: Not only the mere presence of coagulopathy, but also the course of haemostatic alterations following neurotrauma may hold predictive value for patient outcome, irrespective of the severity level of cerebral injury.

Evaluation of Repatriation Parameters: Does Medical History Matter?

BACKGROUND Aeromedical repatriation of patients is an expanding service due to the growing number of travelers worldwide. Of these repatriated patients, a small number require specialized transportation due to severe medical complications. We evaluated the medical in-flight records of Dutch patients with severe disease or polytrauma who were repatriated by air from 1998 to 2002 via one of the largest Dutch alarm centers. We questioned how this Dutch population of repatriated patients is demographically distributed and whether this population is a priori at high risk for acute medical complications that need specialized medical attention. RESULTS Seventy-seven of 115 repatriated patients were 50 years and older, of which most were male (73%). Fifty patients had no significant medical history, whereas the remaining 65 patients suffered from comorbidities such as cardiovascular disease or cancer. In patients aged 18 to 49 years, one third of all patients were repatriated due to traumatic fractures. In the older age category, the main reasons for repatriation were cardiopulmonary incidents. There was an equal distribution in the primary medical reason for repatriation as defined by need for trauma/neurological support and ventilation or circulatory support. Of note, 82% of the 65 patients who traveled with a chronic disease condition were repatriated due to worsening of this particular condition. CONCLUSIONS The present study shows that an aeromedical repatriation service is frequently employed by travelers with a history of chronic disease who develop medical complications. The growing number of repatriated elderly patients and/or patients with preexisting comorbidities requires development of secure pretravel risk assessment and adaptation of the medical service level in foreign countries.

Etomidate and seizure duration in electroconvulsive therapy: is there a dose-dependent relation?

Objective The objective of this study was to determine if there is a dose-dependent relation between etomidate and motor and electroencephalogram (EEG) seizure duration in electroconvulsive therapy (ECT). Methods Seventy-four patients who received at least 3 ECT treatments with etomidate as an anesthetic were included. The association between seizure duration established by EEG and the cuff method, and etomidate dose (in mg/kg) was assessed retrospectively within individual patients, using mixed-effects model analysis with random intercept and random slope. Generalized estimating equation analysis was used to assess whether chances of reaching an adequate seizure depended on dose. Results A small negative association between dose of etomidate and motor and EEG seizure duration was found with a maximum correlation of −0.21. This correlation is considered weak and therefore lacks clinical significance. Higher doses of etomidate decreased the chances of an adequate seizure with an odds ratio of 0.68 per 0.1-mg/kg increase in etomidate (95% confidence interval, 0.52 – 0.90, P-value: 0.007). With a maximum dose of 0.3 mg/kg, 94.1% of the seizures were adequate (95% confidence interval, 91.0–96.2). Conclusions Our data confirm that there is no clinically relevant dose-dependent relation between etomidate and seizure duration in ECT when etomidate is administered as advised in current international guidelines.