Emicizumab does not interfere with the activated clotting time.

INTRODUCTION: The activated clotting time (ACT) is a useful marker of unfractionated heparin (UFH) activity during cardiopulmonary bypass (CPB) or cardiac catheterization. Emicizumab, recently approved for bleeding prevention in haemophilia A patients, acts like FVIII but does not need prior activation; it therefore shortens coagulation times in assays using intrinsic pathway activators and so is expected to shorten the ACT. AIM: To evaluated emicizumab's impact on heparin-induced ACT (Hemochron®) prolongation. METHODS: We measured the high-range (HR) ACT in citrated blood samples from healthy donors (HDs) (n = 9), CPB patients (n = 3) and emicizumab-treated patients (n = 5) after spiking with UFH and/or emicizumab. The low range (LR) ACT was also measured in spiked-samples from HDs and emicizumab-treated patients. RESULTS: In HDs, the median [interquartile range] baseline HR-ACTs were similar with and without emicizumab (129 [123-138] and 136 [115-141] s for 50 µg/ml, respectively); whatever the concentration of emicizumab (10 to 50 µg/ml), increasing the UFH concentration (1-5 UI/ml) prolonged the HR-ACT. In blood from patients undergoing CPB, the HR-ACT prolongation observed during this procedure was not masked by emicizumab at any concentration. Likewise, the addition of increasing concentrations of UFH to blood from emicizumab-treated patients induced a concentration-dependent prolongation of HR-ACT. Baseline LR-ACT were prolonged in emicizumab-treated patients but as for HR-ACT, emicizumab does not prevent heparin-induced prolongation of LR-ACT. CONCLUSION: Emicizumab does not interfere with UFH-induced ACT prolongation. The hemochron® ACT can be used to monitor UFH in patients receiving emicizumab during CPB or cardiac catheterization.

Analgesia nociception index as a tool to predict hypotension after spinal anaesthesia for elective caesarean section.

Arterial hypotension is the main disadvantage of spinal anaesthesia (SA) for caesarean delivery with deleterious effects on maternal-foetal outcomes. Recently, a non-invasive device 'analgesia nociception index' (ANI) has been developed to evaluate the parasympathetic component of the nervous autonomous system. The aim of this study was to evaluate the ability of ANI to predict the risk of hypotension after SA for elective caesarean section. One hundred patients scheduled for elective caesarean delivery under SA were recruited in this observational prospective study. Hemodynamic and ANI parameters were recorded in supine position (TB), in sitting position (T0), after induction of SA (T1) and then every three minutes (T2, T3, Tn) until the end of surgery or having resort to ephedrine. After SA, women were classified into two groups according to occurrence of hypotension (group H, n = 80) or not (group C, n = 20). The variations of ANI between T2 and T0 were significantly higher in the group H as compared to the control group. A threshold of 4.5 points decrease in instantaneous ANI value could predict maternal hypotension. ANI is a simple and effective tool in predicting the risk of SA-related hypotension.Impact statementWhat is already known on this subject? Arterial hypotension is the main disadvantage of spinal anaesthesia for caesarean delivery with deleterious effects on maternal-foetal outcomes. The balance between the sympathic and parasympathic systems could be used to predict the onset of hypotension following spinal anaesthesia. Analgesia nociception index (ANI) is an index calculated based on heart rate variability HRV analysis, designed originally to evaluate the antinociception/Nociception balance.What do the results of this study add? We have shown that the analysis of HRV with ANI was a predictor of maternal hypotension after spinal anaesthesia.What are the implications of these findings for clinical practice and/or further research? ANI is an effective tool in predicting the risk of spinal anaesthesia-related hypotension. These findings are of potential clinical importance in the obstetrical anaesthesia setting. Further studies are required in order to implement this simple tool and optimise prophylactic measures especially vasopressors.

Efficacy and safety of Parecoxib for prevention of catheter-related bladder discomfort in patients undergoing transurethral resection of bladder tumor: Prospective randomised trial.

BACKGROUND AND AIMS: Catheter-related bladder discomfort (CRBD) is the urge to void or discomfort in the suprapubic region secondary to an indwelling urinary catheter. We aimed to evaluate the safety and efficacy of single-dose of intravenous parecoxib in reducing the incidence and severity of CRBD in patients undergoing transurethral resection of bladder tumor (TURBT). METHODS: Sixty-one adult patients, American Society of Anesthesiologists physical status I or II, undergoing elective TURBT under spinal anaesthesia, were randomly allocated to receive 40 mg of IV parecoxib (group P; n = 29) or an equal volume of normal saline (control group C; n = 32). CRBD was graded as none, mild, moderate, and severe. Between-group comparisons were made for the incidence and severity of CRBD, postoperative Visual analog scales (VAS), rescue analgesia equirements, and occurrence of adverse events. Statistical analysis done with the Mann-Whitney U-test and Fisher's Exact Test. A P value of ≤ 0.05 was considered statistically significant. RESULTS: Parecoxib significantly reduced the incidence and severity of CRBD at 2, 4, 6, and 12 hours postoperatively compared to placebo (P < 0.05). Median pain VAS scores were lower in the P group at all times except the first hour. Rescue analgesia was given to more patients in group C (16/32, 50%) than in group P (1/29) (P < 0.001). None of the patients who received parecoxib experienced an adverse event. CONCLUSION: A single intravenous injection of parecoxib is safe and effective in decreasing the incidence and severity of CRBD in patients undergoing TURBT. TRIAL REGISTRATION IDENTIFIER: NCT02729935(www.clinicaltrials.gov).

Pain Measurement in Mechanically Ventilated Patients with Traumatic Brain Injury: Behavioral Pain Tools Versus Analgesia Nociception Index.

INTRODUCTION: Pain is highly prevalent in critically ill trauma patients, especially those with a traumatic brain injury (TBI). Behavioral pain tools such as the behavioral pain scale (BPS) and critical-care pain observation tool are recommended for sedated noncommunicative patients. Analysis of heart rate variability (HRV) is a noninvasive method to evaluate autonomic nervous system activity. The analgesia nociception index (ANI) device (Physiodoloris®, MDoloris Medical Systems, Loos, France) allows noninvasive HRV analysis. The ANI assesses the relative parasympathetic tone as a surrogate for antinociception/nociception balance in sedated patients. The primary aim of our study was to evaluate the effectiveness of ANI in detecting pain in TBI patients. The secondary aim was to evaluate the impact of norepinephrine use on ANI effectiveness and to determine the correlation between ANI and BPS. METHODS: We performed a prospective observational study in 21 deeply sedated TBI patients. Exclusion criteria were nonsinus cardiac rhythm; presence of pacemaker; atropine or isoprenaline treatment; neuromuscular blocking agents; and major cognitive impairment. Heart rate, blood pressure, and ANI were continuously recorded using the Physiodoloris® device at rest (T1), during (T2), and after the end (T3) of the painful stimulus (tracheal suctioning). RESULTS: In total, 100 observations were scored. ANI was significantly lower at T2 (Median [min - max] 54.5 [22-100]) compared with T1 (90.5 [50-100], P < 0.0001) and T3 (82 [36-100], P < 0.0001). Similar results were found in the subgroups of patients with (65 measurements) or without (35) norepinephrine. During procedure, a negative linear relationship was observed between ANI and BPS (r2 = -0.469, P < 0.001). At the threshold of 50, the sensitivity and specificity of ANI to detect patients with BPS ≥ 5 were 73% and 62%, respectively, with a negative predictive value of 86%. DISCUSSION: Our results suggest that ANI is effective in detecting pain in ventilated sedated TBI patients, including those patients treated with norepinephrine.