Novel method for intraoperative assessment of cerebral autoregulation by paced breathing

Background. Cerebral autoregulation (CA) is the mechanism that maintains constancy of cerebral blood flow (CBF) despite variations in blood pressure (BP). Patients with attenuated CA have been shown to have an increased incidence of peri-operative stroke. Studies of CA in anaesthetized subjects are rare, because a simple and non-invasive method to quantify the integrity of CA is not available. In this study, we set out to improve non-invasive quantification of CA during surgery. For this purpose, we introduce a novel method to amplify spontaneous BP fluctuations during surgery by imposing mechanical positive pressure ventilation at three different frequencies and quantify CA from the resulting BP oscillations. Methods. Fourteen patients undergoing sevoflurane anaesthesia were included in the study. Continuous non-invasive BP and transcranial Doppler-derived CBF velocity (CBFV) were obtained before surgery during 3 min of paced breathing at 6, 10, and 15 bpm and during surgery from mechanical positive pressure ventilation at identical frequencies. Data were analysed using frequency domain analysis to obtain CBFV-to-BP phase lead as a continuous measure of CA efficacy. Group averages were calculated. Values are means (sd), and P <0.05 was used to indicate statistical significance. Results. Preoperative vs intraoperative CBFV-to-BP phase lead was 43 (9) vs 45 (8)A degrees, 25 (8) vs 24 (10)A degrees, and 4 (6) vs -2 (12)A degrees during 6, 10, and 15 bpm, respectively (all P=NS). Conclusions. During surgery, cerebral autoregulation indices were similar to values determined before surgery. This indicates that CA can be quantified reliably and non-invasively using this novel method and confirms earlier evidence that CA is unaffected by sevoflurane anaesthesia. Clinical trial registration. NCT0307143

Sevoflurane based anaesthesia does not affect already impaired cerebral autoregulation in patients with type 2 diabetes mellitus

Background: The baroreflex regulates arterial blood pressure (BP). During periods when blood pressure changes, cerebral blood flow (CBF) is kept constant by cerebral autoregulation (CA). In patients with diabetes mellitus (DM), low baroreflex sensitivity (BRS) is associated with impaired CA. As sevoflurane-based anaesthesia obliterates BRS, we hypothesised that this could aggravate the already impaired CA in patients with DM resulting in a ‘double-hit’ on cerebral perfusion leading to increased fluctuations in blood pressure and cerebral perfusion. Methods: On the day before surgery, we measured CBF velocity (CBFV), heart rate, and BP to determine BRS and CA efficacy (CBFVmean-to-BPmean-phase lead) in 25 patients with DM and in 14 controls. During the operation, BRS and CA efficacy were determined during sevoflurane-based anaesthesia. Patients with DM were divided into a group with high BRS (DMBRS↑) and a group with low BRS (DMBRS↓). Values presented are median (inter-quartile range). Results: Preoperative vs intraoperative BRS was 6.2 (4.5–8.5) vs 1.9 (1.1–2.5, P<0.001) ms mm Hg−1 for controls, 5.8 (4.9–7.6) vs 2.7 (1.5–3.9, P<0.001) ms mm Hg−1 for patients with DMBRS↑, and 1.9 (1.5–2.8) vs 1.1 (0.6–2.5, P=0.31) ms mm Hg−1 for patients with DMBRS↓. Preoperative vs intraoperative CA efficacy was 43° (38–46) vs 43° (38–51, P=0.30), 44° (36–49) vs 41° (32–49, P=0.52), and 34° (28–40) vs 30° (27–38, P=0.64) for controls, DMBRS↑, and DMBRS↓ patients, respectively. Conclusions: In diabetic patients with low preoperative BRS, preoperative CA efficacy was also impaired. In controls and diabetic patients, CA was unaffected by sevoflurane-based anaesthesia. We therefore conclude that sevoflurane-based anaesthesia does not contribute to a ‘double-hit’ phenomenon on cerebral perfusion. Clinical trial registration: NCT 03071432

Cerebral oxygenation during changes in vascular resistance and flow in patients on cardiopulmonary bypass - a physiological proof of concept study

Despite a rise in blood pressure, cerebral oxygenation decreases following phenylephrine administration, and we hypothesised that phenylephrine reduces cerebral oxygenation by activating cerebral alpha 1 receptors. We studied patients on cardiopulmonary bypass during constant flow. Phenylephrine raised mean arterial pressure (alpha(1)-mediated) from mean (SD) 69 (8) mmHg to 79 (8) mmHg; p = 0.001, and vasopressin raised mean arterial pressure (V-1 mediated) from 69 (8) mmHg to 83 (6) mmHg; p = 0.001. Both drugs elicited a comparable decrease in cerebral oxygenation from 61 (7)% to 60 (7)%; p = 0.023 and 61 (8)% to 59 (8)%; p = 0.022, respectively. This implies that after phenylephrine or vasopressin administration, cerebral oxygenation declines as a result of cerebral vasoconstriction, due to either both cerebral a(1) and V-1 receptors being equipotentially activated or to an intrinsic myogenic mechanism of cerebral vasculature in reaction to blood pressure elevatio

Suspected common bile duct stones: reduction of unnecessary ERCP by pre-procedural imaging and timing of ERCP

Background: Endoscopic retrograde cholangiopancreatography (ERCP) is the procedure of choice to remove sludge/stones from the common bile duct (CBD). In a small but clinically important proportion of patients with suspected choledocholithiasis ERCP is negative. This is undesirable because of ERCP associated morbidity. We aimed to map the diagnostic pathway leading up to ERCP and evaluate ERCP outcome. Methods: We established a prospective multicenter cohort of patients with suspected CBD stones. We assessed the determinants that were associated with CBD sludge or stone detection upon ERCP. Results: We established a cohort of 707 patients with suspected CBD sludge or stones (62% female, median age 59 years). ERCP was negative for CBD sludge or stones in 155 patients (22%). Patients with positive ERCPs frequently had pre-procedural endoscopic ultrasonography (EUS) or magnetic resonance cholangiopancreatography (MRCP) imaging (44% vs. 35%; P = 0.045). The likelihood of ERCP sludge and stones detection was higher when the time interval between EUS or MRCP and ERCP was less than 2 days (odds ratio 2.35; 95% CI 1.25–4.44; P = 0.008; number needed to harm 7.7). Conclusions: Even in the current era of society guidelines and use of advanced imaging CBD sludge or stones are absent in one out of five ERCPs performed for suspected CBD stones. The proportion of unnecessary ERCPs is lower in case of pre-procedural EUS or MRCP. A shorter time interval between EUS or MRCP increases the yield of ERCP for suspected CBD stones and should, therefore, preferably be performed within 2 days before ERCP. Graphical abstract: [Figure not available: see fulltext.]

The geography of future water challenges: Bending the trend

Industrial EcologyEnvironmental Biolog