Haemodynamic effects of remifentanil during induction of general anaesthesia with propofol. A randomised trial.

BACKGROUND: Remifentanil may have a dose-dependent haemodynamic effect during the induction of general anaesthesia combined with propofol. Our objective was to investigate whether systolic arterial blood pressure (SAP) was reduced to a greater extent when the remifentanil dose was increased. METHODS: This randomised, double-blind, dose-controlled study was conducted at the Day Surgery Unit of Haugesund Hospital, Norway. Ninety-nine healthy women scheduled for gynaecological surgery were randomly allocated in a 1:1:1 ratio to receive remifentanil induction with a low, medium or high dose corresponding to maximum effect-site concentrations (Ce) of 2, 4 and 8 ng/mL. The induction dose of propofol was 1.8 mg/kg, with a Ce of 2.9 µg/mL. Anaesthesia was induced using target-controlled infusion. After 150 s of sedation, a bolus of remifentanil and propofol was administered. Baseline was defined as 55-5 s before the bolus dose, and the total observation time was 450 s. We used beat-to-beat haemodynamic monitoring with LiDCOplus. The primary outcome variable was the maximum decrease in SAP within 5 min after bolus administration of remifentanil and propofol. Absolute and relative changes from baseline to minimal values and the area under the curve (AUC) were used as effect measures. Comparisons of groups were performed using analysis of variance (ANOVA). RESULTS: Median remifentanil doses were 0.75, 1.5 and 3.0 µg/kg in the low-, medium- and high-dose groups, respectively. The absolute changes (mean ± standard deviation) in SAP in the low-, medium- and high-dose groups of remifentanil were -39 ± 9.6 versus -43 ± 9.1, and -41 ± 10 mmHg, respectively. No difference (95% confidence interval) in the absolute change in SAP was observed between the groups (ANOVA, p = .29); medium versus low dose 3.7 (-2.0, 9.4) mmHg, and high versus medium dose -2.2 (-8.0; 3.5) mmHg. The relative changes from baseline to minimum SAP values were -30% versus -32% versus -32% (p = .52). The between-group differences in the AUC were not statistically significant. Relative changes in heart rate (-20% vs. -21% vs. -21%), stroke volume (-19% vs. -16% vs. -16%), cardiac output (-32% vs. -32% vs. -32%), systemic vascular resistance (-24% vs. -27% vs. -28%), and AUC were not statistically significant. CONCLUSION: This trial demonstrated major haemodynamic changes during the induction of anaesthesia with remifentanil and propofol. However, we did not observe any statistically significant differences between low, medium or high doses of remifentanil when using continuous invasive high-accuracy beat-to-beat monitoring.

Hemodynamic effects of a low versus a high dose of propofol during induction of anesthesia. A randomized trial.

BACKGROUND: Hypotension is common after anesthesia induction with propofol and is associated with increased morbidity. It is important to examine the effects of the proposed interventions to limit preventable hypotension, as suggested by the reduction in the dose of propofol. Our objective was to investigate whether a high dose of propofol is inferior to a low dose with respect to changes in systolic arterial blood pressure (SAP). METHODS: This randomized, double-blind, dose-controlled, non-inferiority study included 68 healthy women scheduled for gynecological surgery at the Day Surgery Unit, Haugesund Hospital, Norway. The patients were randomly allocated 1:1 to a low or high dose (1.4 mg/kg total body weight (TBW) versus 2.7 mg/kg TBW of propofol corresponding to maximal effect site concentrations (Ce) of 2.0 µg/mL versus 4.0 µg/mL. The dose of remifentanil was 1.9-2.0 µg/kg TBW, with maximal Ce of 5.0 ng/mL. The patients were observed for 450 s from the start of the infusions. The first 150 s was the sedation period, after which a bolus of propofol and remifentanil was administered. Baseline was defined as 55-5 s before the bolus doses. LiDCOplus was used for invasive beat-to-beat hemodynamic monitoring of changes in SAP, heart rate (HR), cardiac output (CO), stroke volume (SV), and systemic vascular resistance (SVR). A difference of 10 mmHg in the change in SAP was considered to be clinically important. RESULTS: The SAP change difference for low versus high dose was -2.9 mmHg (95% CI -9.0-3.1). The relative changes for low versus high dose were SAP -31% versus -36%, (p < .01); HR -24% versus -20%, (p = .09); SVR -20% versus -31%, (p < .001); SV -16% versus -20%, (p = .04); and CO -35% versus -32%, (p = .33). CONCLUSION: A high dose of propofol was not inferior to a low dose, and a reduction in the dose of propofol did not result in clinically important attenuation of major hemodynamic changes during induction in healthy women. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT03861364, January 3, 2019.

Haemodynamic stability after paracervical block: A randomized, controlled, double-blind study comparing bupivacaine-adrenaline with bupivacaine.

BACKGROUND: Paracervical block is widely used in gynaecological interventions on cervix and uterus. Many surgeons add adrenaline 100 µg or pitressin 3-5 IU in a total volume of 10-20 mL to reduce total blood loss. We wanted to examine haemodynamic stability in healthy patients given bupivacaine with and without adrenaline. METHODS: In this randomised, double-blinded, controlled study, 30 healthy women scheduled for cervical conisation got a paracervical block using bupivacaine 50 mg with adrenaline 100 µg (BA-group, n = 14) or without adrenaline (B-group, n = 16) after induction of general anaesthesia. LiDCOplus was used for minimally invasive haemodynamic monitoring. Changes in cardiac output (CO) and systolic blood pressure (SBP) were the primary outcome. Changes in heart rate (HR), stroke volume (SV), and systemic vascular resistance (SVR) were secondary outcome variables. Area under the curve (AUC) ratios and change from baseline to maximal values were used as effect measures comparing the two groups. RESULTS: The AUC-ratio for CO and SBP was 2.50 (P < 0.001) and 1.70 (P = 0.03), respectively. For HR, SV, and SVR the AUC-ratio was 1.59 (P < 0.01), 1.52 (P < 0.001), and 0.90 (P = 0.14), respectively. CO increased 68% (standard deviation (SD) 42%, P < 0.001), HR increased 41% (SD 26%, P < 0.001), and SV increased 26% (SD 17%, P < 0.001) from baseline to maximal values after 70-90 seconds in the BA-group. CONCLUSION: Paracervical block with bupivacaine 50 mg and adrenaline 100 µg may give haemodynamic instability in healthy females and is not recommended if haemodynamic side effects are to be avoided.

Hemodynamics of Phenylephrine Infusion Versus Lower Extremity Compression During Spinal Anesthesia for Cesarean Delivery: A Randomized, Double-Blind, Placebo-Controlled Study.

BACKGROUND: Phenylephrine infusion is the current first-line choice for prevention of spinal hypotension during cesarean delivery. The optimal dosage regimen is still undetermined. A mechanical alternative, lower limb wrapping, has been examined in a few small studies showing moderate success. In this trial, we compared the effect of leg wrapping with low-dose phenylephrine infusion and with placebo treatment on systolic arterial blood pressure during spinal anesthesia for cesarean delivery. METHODS: In this randomized, double-blinded, placebo-controlled study, healthy women received either phenylephrine (n = 38; initial bolus of 0.25 µg kg and infusion of 0.25 µg kg min), leg wrapping (n = 38), or no treatment (control; n = 36) during spinal anesthesia for elective cesarean delivery. LiDCOplus was used for continuous minimally invasive hemodynamic monitoring. The extent of decrease in systolic arterial blood pressure (for 13 minutes after spinal induction) was the primary outcome. Cardiac output, systemic vascular resistance, stroke volume, heart rate, neonatal acid-base status, and Apgar score were secondary outcome variables. Mixed model analysis of continuous hemodynamic trends during the first 13 minutes after induction of spinal anesthesia was performed. RESULTS: In the phenylephrine group, the decrease in systolic arterial blood pressure was significantly less (difference in rate of change, 0.09 mm Hg 5 s; 95% confidence interval, 0.02-0.16; P = 0.013); systemic vascular resistance (P < 0.001) was significantly higher; stroke volume (P = 0.41) was similar; and heart rate (P = 0.002) and cardiac output (P < 0.001) were significantly lower compared with the leg wrapping group. Compared with control, the leg wrapping group had a significantly smaller decrease in systolic arterial blood pressure (0.39 mm Hg 5 s; 95% confidence interval, 0.32-0.46; P < 0.001), higher stroke volume (P < 0.001), and higher cardiac output (P = 0.001). CONCLUSIONS: An initial bolus of phenylephrine followed by a low-dose phenylephrine infusion was superior to leg wrapping and no intervention for the prevention of hypotension during spinal anesthesia for cesarean delivery. Phenylephrine prevented hypotension primarily by restoring systemic vascular resistance and did not cause hypertension or a clinically relevant reduction in cardiac output. Leg wrapping prevented hypotension compared with no intervention by limiting modest early spinal anesthesia-mediated venodilation.

Changes in blood pressure and cardiac output during cesarean delivery: the effects of oxytocin and carbetocin compared with placebo.

BACKGROUND: Little is known about maternal hemodynamics after Cesarean delivery. Uterine contractions may increase cardiac output. Oxytocin is the first-line treatment for uterine atony, although the effects of the long-acting oxytocin analogue carbetocin are comparable with that of oxytocin. The authors analyzed the effects of i.v. oxytocin 5 U, carbetocin 100 µg, and placebo on hemodynamics, uterine tone, adverse events, and blood loss after Cesarean delivery. METHODS: This was a randomized, double-blinded, placebo-controlled, parallel-group comparison of carbetocin and oxytocin after elective Cesarean delivery of singletons under spinal anesthesia (n = 76). Continuously measured invasive systolic arterial pressure was the primary outcome measure. RESULTS: The mean systolic arterial pressure decrease was 28 mmHg (95% CI, 22-34) after oxytocin and 26 mmHg (95% CI, 20-31) after carbetocin. The decrease was greatest after 80 (95% CI, 71-89) and 63 s (95% CI, 55-72), respectively (P = 0.006). The differences were nearly undetectable after 2.5 min, although the effect of carbetocin was slightly greater than placebo (P < 0.001). The group differences in systolic arterial pressure decreased over 5 min and were gone at 1 h. Heart rate and cardiac output increased in all three groups. Stroke volume increased after oxytocin and carbetocin but was unchanged after placebo. CONCLUSIONS: The hemodynamic side effects of oxytocin 5 U and carbetocin 100 µg were comparable. The lack of an increase in stroke volume in the placebo group challenges the theory that uterine contraction causes autotransfusion of uterine blood, leading to an increase in preload.