Florent Laverdure

PF4-heparin antibodies during ECMO: incidence, course, and outcomes.

Unfractionated heparin is the first-line anticoagulant treatment during extracorporeal membrane oxygenation (ECMO). Heparin-induced thrombocytopenia (HIT) is a rare but severe complication [1] and is challenging to diagnose after cardiopulmonary bypass [2]. The first-line laboratory test for diagnosing HIT is detection of PF4heparin antibodies (PF4-H) [1]. This test is highly sensitive [1] but lacks specificity after cardiopulmonary bypass [3]. The incidence and course of PF4-H positivity during ECMO remain unknown. Here we reported the incidence of PF4-H positivity over time in patients under ECMO, the relationship with HIT, and the outcomes of patients. Our institutional review board approved the study. Consecutive patients managed with ECMO for at least 72 h were identified prospectively and underwent PF4-H assays (Electronic Supplement Fig. 1). Patients were divided according to PF4-H positivity. A diagnosis of HIT needs a positive functional assay [2]. The 73 studied patients had 320 PF4-H assays performed. Among them, 22 (30.1 %; 95 % CI, 20.2–42.1) had at least one positive PF4-H assay. Characteristics and outcomes of patients are summarized in Table 1. Mean time from ECMO initiation to PF4-H seroconversion was 5.1 ± 3.5 days (0.0–13.0 days). Optical densities of positive PF4-H assays varied significantly over time, peaking between days 4 and 6 (1.10 ± 0.83 units). HIT was diagnosed in 3 (4.1 %; 95 % CI, 1.4–11.4) patients. The frequency of thrombotic events increased with the PF4-H titer, from 7/52 (13.5 %) when optical densities were less than 0.5 to 2/9 (22.2 %) when optical densities were between 0.5 and 1.0, and 7/12 (58.3 %) when optical densities were greater than 1.0 (P = 0.003). Platelet counts varied significantly over time (P < 0.0001), with no difference between patients with and without positive PF4-H (Electronic Supplement Fig. 2). The incidence of PF4-H positivity during ECMO is similar to that observed several days after cardiopulmonary bypass where PF4-H positivity ranged between 26 and 51 % [2, 3]. Although nearly a third of our patients had PF4-H, only 4 % were diagnosed with HIT. This incidence of HIT is higher than previously reported in patients after cardiothoracic surgery [2] or during ECMO [4]. Our work emphasizes the challenges raised by diagnosing HIT in patients receiving ECMO. The time-course of the platelet count was not discriminant [2, 3] and the 4Ts score failed to discriminate patients with and without positive PF4-H. During ECMO, a positive PF4-H assay, even with high optical density values, is not sufficient to diagnose HIT. Therefore, the diagnosis of HIT should be confirmed by a functional assay to avoid overdiagnosis [1]. However, receiver operating characteristics of functional assays during ECMO are unknown. We agree that serotonin release assay should be used when the PF4-H and platelet aggregation test results are discordant [2]. Importantly, a negative PF4-H assay rules out HIT [1]. Association between PF4-H positivity and thrombotic events has been previously reported [5] as PF4 itself can be prothrombotic. Patients with positive PF4-H had a trend toward higher mortality as previously reported [4]. However, the clinical comorbidities associated with the risk of death should be also taken into account [2, 4].

Fiber optic bronchoscopy and remifentanil target-controlled infusion in critically ill patients with acute hypoxaemic respiratory failure: A descriptive study

INTRODUCTION Sedation optimizes patient comfort and ease of execution during fiber optic bronchoscopy (FOB). Our objective was to describe the safety and efficacy of remifentanil-TCI during FOB in non-intubated, hypoxaemic, thoracic surgery ICU patients. METHODS Consecutive spontaneously breathing adults requiring FOB after thoracic surgery were included if they had hypoxaemia (PaO2/FiO2<300mmHg or need for non-invasive ventilation [NIV]) and prior FOB failure under topical anaesthesia. The remifentanil initial target was chosen at 1ng/mL brain effect-site concentration (Cet), then titrated to 0.5ng/mL Cet increments according to patient comfort and coughing. Outcomes were patient-reported pain and discomfort (Visual Analogue Scale scores), ventilatory support intensification within 24hours after bronchoscopy, and ease of FOB execution. RESULTS Thirty-nine patients were included; all had a successful FOB. Their median PO2/FiO2 before starting FOB was 187±84mmHg and 24 patients received NIV. Median [interquartile range] pain scores were not different before and after FOB (1.0 [0.0-3.0] and 0.0 [0.0-2.0], respectively). Discomfort was reported as absent or minimal by 27 patients (69%; 95% confidence interval [95% CI], 54-81%) and as bothersome but tolerable by 12 patients (31%; 95% CI, 19-46%). Mean FiO2 returned to baseline within 2hours after FOB in 30 patients; the remaining 9 patients (23%; 95% CI, 13-38%) received ventilatory support intensification. Ease of execution was good or very good in 34 patients (87%; 95% CI, 73-94%), acceptable in 4 patients, and poor in 1 patient (persistent cough). CONCLUSION Sedation with remifentanil-TCI during FOB with prior failure under topical anaesthesia alone was effective and acceptably safe in non-intubated hypoxaemic thoracic surgery patients.

Evaluation of Reperfusion Pulmonary Edema by Extravascular Lung Water Measurements After Pulmonary Endarterectomy.

Objectives: Reperfusion pulmonary edema is a specific complication of pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension. Extravascular lung water measurement may be valuable for diagnosing reperfusion pulmonary edema. The primary objective of this study was to describe and assess the clinical significance of extravascular lung water variations after pulmonary endarterectomy. Design: Prospective observational study. Setting: Nineteen-bed cardiothoracic ICU. Patients: Consecutive patients who were hemodynamically stable after pulmonary endarterectomy were divided into two groups based on whether their preoperative pulmonary vascular resistance indicated severe or nonsevere chronic thromboembolic pulmonary hypertension (> 900 or ⩽ 900 dynes·s/cm5, respectively). Interventions: Hemodynamic variables obtained by right heart catheterization and transpulmonary thermodilution measurements were recorded 1 hour, 1 day, and 2 days after pulmonary endarterectomy. Extravascular lung water was indexed to predicted body weight (EVLWPBW). Measurements and Main Results: We studied 31 patients. Overall, 26 patients (84%) experienced reperfusion pulmonary edema during the first 72 hours after pulmonary endarterectomy. EVLWPBW significantly increased between the first hour after pulmonary endarterectomy and day 2 (10.2 ± 2.6 vs 11.4 ± 3.6; p = 0.03). EVLWPBW measured at the first hour after pulmonary endarterectomy is closely associated with reperfusion pulmonary edema occurrence in the next 48 hours (area under the receiver-operating characteristics curve = 0.88 ± 0.07). EVLWPBW correlated with duration of mechanical ventilation (&rgr; = 0.59; p < 0.0001) and ICU stay (&rgr; = 0.52; p < 0.0001). Patients with severe chronic thromboembolic pulmonary hypertension (n = 15) had higher EVLWPBW values at day 2 compared with those without (n = 16) (13.2 ± 3.6 vs 9.7 ± 2.7 mL/kg; p = 0.004). Cardiac output was measured simultaneously by pulmonary artery catheter and aortic transpulmonary thermodilution on 92 occasions; agreement was good, with a bias of 0.50 ± 0.95 L/min (95% CI, –1.36–2.36). Conclusions: Accurate extravascular lung water measurements were obtained after pulmonary endarterectomy. Extravascular lung water may prove valuable for diagnosing reperfusion pulmonary edema after pulmonary endarterectomy and had prognostic value. Extravascular lung water values were significantly higher in patients with severe compared with nonsevere chronic thromboembolic pulmonary hypertension.