MACBAR Of Sevoflurane Research Articles

Effects of Etco2 on the Minimum Alveolar Concentration of Sevoflurane that Blunts the Adrenergic Response to Surgical Incision: A Prospective, Randomized, Double-Blinded Trial.

CO2 has anesthetic potency and effectively influences the circulatory system. We investigated the effects of Etco2 on the minimum alveolar concentration of sevoflurane that blunts the adrenergic response to surgical incision (MAC-BAR) in patients undergoing radical surgery for gastric carcinoma. Ninety patients undergoing radical gastric-carcinoma surgery under general anesthesia were enrolled and randomly assigned into 3 groups. After intubation, the Etco2 in group L (n = 30), group N (n = 30), and group H (n = 30) was adjusted to 25 mm Hg ≤ Etco2 <30 mm Hg, 30 mm Hg ≤ Etco2 < 40 mm Hg, and 40 mm Hg ≤ Etco2 < 45 mm Hg, respectively, by changes in controlled ventilation. Hemodynamics and depth of anesthesia were observed before and after skin incision. The MAC-BAR of sevoflurane for each group was determined using an up-and-down sequential-allocation technique. To obtain 7 crossovers, 25, 26, and 26 patients were used in group L, group N, and group H, respectively. The MAC-BAR of sevoflurane using the up-and-down method for group H was significantly lower than that for group L (2.3% [95% confidence interval {CI}, 2.2-2.4] vs 2.9% [95% CI, 2.7-3.0]; difference, -0.6% [95% CI, -0.7 to -0.4], P < .001) and group N (2.3% [95% CI, 2.2-2.4] vs 2.8% [95% CI, 2.8-2.9]; difference, -0.5% [95% CI, -0.7 to -0.4], P < .001), while no significant difference was found between group L and group N (P = 1.000). Higher Etco2 levels (Etco2 values equal to 40 mm Hg or higher) can effectively decrease the MAC-BAR of sevoflurane in patients undergoing radical surgery for gastric carcinoma.

Effects of different plasma target concentrations of remifentanil on the MACBAR of sevoflurane in children with laparoscopic surgery

BackgroundTo investigate the effects of different plasma target concentrations of remifentanil on the minimum alveolar concentration (MAC) for blocking adrenergic response (BAR) of sevoflurane in children with laparoscopic herniorrhaphy.MethodsSeventy-five children with 3-7 years old scheduled for laparoscopic herniorrhaphy were randomly divided into group R0, group R1, and group R2 according to different remifentanil plasma target concentration (0, 1, and 2 ngml-1), respectively. The MACBAR of sevoflurane was determined by the up-and-down and sequential method in each group. The concentrations of epinephrine and noradrenaline were also determined at corresponding time points.ResultsA total of 52 child patients were used among the anticipated 75 patients. In groups R0, R1, and R2, the MACBAR of sevoflurane was (3.29 ± 0.17) %, (2.12 ± 0.10) % and (1.29 ± 0.11) %, respectively, and a significant difference was found among the three groups (P<0.05). The changes of epinephrine and noradrenaline concentrations in each group before and after insufflation of carbon dioxide pneumoperitoneum showed no significant differences.ConclusionRemifentanil by target-controlled infusion can effectively reduce the MACBAR of sevoflurane during laparoscopic surgery in children. At a similar effect of MACBAR, both the changes of epinephrine and noradrenaline concentrations are not affected by the infusion of different remifentanil target concentrations.Trial registrationThe trial was registered at http://www.chictr.org.cn(ChiCTR1800019393, 8, Nov, 2018).

Effect of low-dose ketamine on MACBAR of sevoflurane in laparoscopic cholecystectomy: A randomized controlled trial.

Low-dose ketamine can reduce the minimum alveolar concentration of sevoflurane necessary to block the adrenergic response (MACBAR ) in animals. However, the effects of low-dose ketamine on the sevoflurane MACBAR in patients undergoing laparoscopic surgery are unclear. The aim of this study was to investigate the effects of three different low doses of ketamine on the MACBAR of sevoflurane in patients undergoing laparoscopic cholecystectomy. One hundred patients who underwent laparoscopic cholecystectomy were enrolled. After general anaesthesia induction and tracheal intubation, patients received sevoflurane anaesthesia in combination with a loading dose of saline followed by infusion or a loading dose of 0.5mg/kg ketamine followed by a continuous infusion of 5 (K1 group), 10 (K2 group) and 20μg/kg/min (K3 group). The target concentration of end-tidal sevoflurane was maintained for at least 20minutes before carbon dioxide pneumoperitoneum stimulus. The MACBAR of sevoflurane in each group was determined by using an up-and-down sequential allocation technique. Seventy-one patients completed the study. The values of MACBAR for sevoflurane were 5.3% in the K0 , 4.8% in K1 , 3.3% in K2 and 3.2% in K3 groups. The use of ketamine significantly reduced the MACBAR of sevoflurane compared to sevoflurane alone. The K2 and K3 groups showed significantly lower values of MACBAR than that in the K1 group. However, a higher dose of ketamine in the K3 group did not further reduce the sevoflurane MACBAR . The mean arterial blood pressure (MAP) values before pneumoperitoneum in the K2 and the K3 groups were significantly higher compared to those in the K0 and K1 groups. Compared with the values before pneumoperitoneum, the heart rate and MAP after pneumoperitoneum were significantly increased. Overall, the haemodynamics remained stable during the study period in all groups. A loading dose of 0.5mg/kg ketamine followed by a continuous infusion of 10.0μg/kg/min led to a significant decrease in the MACBAR of sevoflurane in patients undergoing laparoscopic cholecystectomy.

Effects of different sufentanil target concentrations on the MACBAR of sevoflurane in patients with carbon dioxide pneumoperitoneum stimulus

BackgroundThis study aims to observe the effects of different target controlled plasma sufentanil concentrations on the minimum alveolar concentration (MAC) of sevoflurane for blocking adrenergic response (BAR) in patients undergoing laparoscopic cholecystectomy with carbon dioxide pneumoperitoneum stimulation.MethodsEighty-five patients undergoing laparoscopic cholecystectomy, aged 30–65 years, with American Society of Anesthesiologists physical status I-II, were enrolled in this study. All the patients were randomly divided into 5 groups (S0, S1, S2, S3, S4) with different sufentanil plasma target concentration (0.0, 0.1, 0.3, 0.5, 0.7 ng ml− 1). Anesthesia was induced by inhalation of 8% sevoflurane in 100% oxygen, and 0.6 mg kg− 1 of rocuronium was intravenously injected to facilitate the insertion of a laryngeal mask airway. The end-tidal sevoflurane concentration and sufentanil plasma target concentration were adjusted according to respective preset value in each group. The hemodynamic response to pneumoperitoneum stimulus was observed after the end-tidal sevoflurane concentration had been maintained stable at least for 15 min. The MACBAR of sevoflurane was measured by a sequential method. Meanwhile, epinephrine (E) and norepinephrine (NE) concentrations in the blood were also determined before and after pneumoperitoneum stimulus in each group.ResultsWhen the method of independent paired reversals was used, the MACBAR of sevoflurane in groups S0, S1, S2, S3, S4 was 5.333% (confidence interval [CI] 95%: 5.197–5.469%), 4.533% (95% CI: 4.451–4.616%), 2.861% (95% CI: 2.752–2.981%), 2.233% (95% CI: 2.142–2.324%) and 2.139% (95% CI: 2.057–2.219%), respectively. Meanwhile, when the isotonic regression analysis was used, the MACBAR of sevoflurane in groups S0, S1, S2, S3, S4 was 5.329% (95% CI: 5.321–5.343%), 4.557% (95% CI: 4.552–4.568%), 2.900% (95% CI: 2.894–2.911%), 2.216% (95% CI: 2.173–2.223%) and 2.171% (95% CI: 2.165–2.183%), respectively. The MACBAR was not significantly different between groups S3 and S4 when using 0.5 and 0.7 ng ml− 1 of sufentanil plasma target concentrations. No significant difference was found in the change of E or NE concentration between before and after pneumoperitoneum stimulation in each group.ConclusionsThe MACBAR of sevoflurane can be decreased with increasing sufentanil plasma target concentrations. A ceiling effect of the decrease occurred at a sufentanil plasma target concentration of 0.5 ng ml− 1. When the sympathetic adrenergic response was inhibited in half of the patients to pneumoperitoneum stimulation in each group, the changes of E and NE concentrations showed no significant differences.Trial registrationThe study was registered at http://www.chictr.org.cn (ChiCTR1800015819, 23, April, 2018).

Determination of the minimum alveolar concentration of sevoflurane that blunts adrenergic responses and the effect of a constant rate infusion of ketamine in sheep

Minimizing sympathetic stimulation under anesthesia prevents activation of the neuroendocrine stress response. The minimum alveolar concentration blunting adrenergic responses in 50% of the population when exposed to a noxious stimulus is defined as MAC-BAR. The purpose of this study was to determine the MAC-BAR of sevoflurane (MAC-BARsevo) in sheep and the MAC-BAR sparing effects of ketamine.Thirteen healthy Dorset-cross adult ewes, 4 ± 1 year old and weighing 74 ± 9 kg, were enrolled in a randomized blinded crossover study design. Ewes were anesthetized twice for MAC-BARsevo determination. After face mask induction with sevoflurane, sheep received intravenous ketamine at 1.5 mg/kg and a constant rate infusion of 1.5 mg/kg/h or an equivalent volume of saline (placebo). After 8 day washout, the other treatment was administered. A bracketing technique was used for MAC-BARsevo determination and values were collected in duplicate. The mechanical stimulus (sponge forceps) was applied at the coronary band for 1 min and blood was collected for ketamine plasma concentrations. The MAC-BARsevo values of each treatment were compared using a paired t-test.Mean MAC-BARsevo of the ketamine and placebo were 2.73 ± 0.23% and 2.77 ± 0.31%, respectively and no significant difference was found (p = .638). Average ketamine plasma concentrations was 1.54 ± 0.18 μg/mL maintained through the study.Ketamine at 1.5 mg/kg, followed by 1.5 mg/kg/h, did not decrease the MAC-BARsevo in sheep. Further studies to determine the effect of higher doses of ketamine on inhalational anesthetic agents and their potential adverse effects are warranted.

Effect of remifentanil on MACBAR of sevoflurane in patients with hepatic dysfunction undergoing laparoscopic surgery

Objective To evaluate the effect of remifentanil on the minimum alveolar concentration of sevoflurane required to blunt the adrenergic response (MACBAR) in the patients with hepatic dysfunction undergoing laparoscopic surgery. Methods The patients, aged 18-64 yr, with body mass index < 30 kg/m2, undergoing elective laparoscopic hepatobiliary surgery, were selected.Patients with normal liver function were selected as control group (C group), and patients with liver dysfunction (Child-Pugh grade B) were selected as test group and divided into 3 subgroups by a random number table method: no remifentanil group (R0 group) and different target plasma concentrations of remifentanil groups (R1 group and R2 group). Anesthesia was induced by intravenously injecting propofol 2-3 mg/kg, remifentanil 2 μg/kg and cisatracurium 0.15 mg/kg.After endotracheal intubation, mechanical ventilation was performed.The end-tidal sevoflurane concentration was adjusted to the preset concentration in each group and maintained at the level for 20 min before the pneumoperitoneum was established.Anesthesia was maintained as follows: remifentanil was not used in C group and R0 group, and the target plasma concentration of remifentanil was 1 and 2 ng/ml in group R1 and group R2, respectively, and sevoflurane was inhaled.The MACBAR of sevoflurane was determined using the sequential method.The initial end-tidal sevoflurane concentrations were 5.0%, 4.6%, 2.6% and 2.4% in group C, group R0, group R1 and group R2, respectively.MAP and HR were recorded and blood samples were collected before and after pneumoperitoneum, and the plasma epinephrine and norepinephrine concentrations were measured by enzyme-linked immunosorbent assay, and the difference in MAP and HR before and after pneumoperitoneum was calculated. Results A total of 14 cases in group C, 19 cases in group R0, 19 cases in group R1 and 15 cases in group R2 completed the study.Compared with group C, the MACBAR of sevoflurane and plasma adrenergic concentration before and after pneumoperitoneum were significantly decreased (P 0.05). Compared with group R0, the MACBAR of sevoflurane was significantly decreased in group R1 and group R2, and HR before and after pneumoperitoneum and the difference were significantly decreased in group R2(P<0.05). The MACBAR of sevoflurane was significantly lower in group R2 than in group R1 (P<0.05). Conclusion Remifentanil can decrease the MACBAR of sevoflurane and enhance the efficacy in inhibiting the stress responses in the patients with hepatic dysfunction undergoing laparoscopic surgery. Key words: Anesthetics, inhalation; Piperidines; Hepatic insufficiency; Dose-response relationship, drug

Determination of MACBAR of sevoflurane and evaluation of the effects of a ketamine constant rate infusion on sevoflurane MACBAR in sheep

Determination of MACBAR of sevoflurane and evaluation of the effects of a ketamine constant rate infusion on sevoflurane MACBAR in sheep

Effects of different target remifentanil concentrations on MACBAR of sevoflurane and catecholamineRAR in gynecological patients undergoing laparoscopic surgery

Objective To investigate the effects of different targeted plasma remifentanil concentrations on the minimum alveolar concentration of sevoflurane (MACBAR) and minimum plasma catecholamine concentration for blocking adrenergic response (CatecholamineBAR: NEBR, EBAR) in gynecological patients undergoing laparoscopic surgery using carbon dioxide pneumoperitoneum.Methods Seventy five gynecological patients undergoing laparoscopic surgery, ASA physical status Ⅰ -Ⅱ, were randomly assigned to three groups: control group (R0) and 2 remifentanil groups (R1, R2). Anesthesia was induced by target controlled infusion with remifentanil (plasma concentration 2 μg/L), and intravenous infection with 0.3 mg/kg etomidate. Vecuronium 0.1 mg/kg was administered to facilitate tracheal intubation. After intubation anesthesia was maintained with sevoflurane in all groups. But in R0, R1and R2, the targeted plasma concentration of remifentanil was adjusted to 0, 1 μg/L and 2 μg/L, respectively. The MACBAR of sevoflurane was determined by using a sequential design and pneumoperitoneum stimulation in each group, while blood samples were collected at corresponding time points to determinate catecholamine concentrations and the values of NEBAR, EBAR were calculated.Results In group R0, R1 and R2, the MACBARs of sevoflurane were (4.60±0.30)％, (2.37±0.21) ％ and(1.70±0.28) ％, respectively.No significant differences were found in NEBAR, EBAR and minimum MAP among the three groups. Conclusion The targeted plasma concentrations of remifentanil at 1 μg/L and 2 μg/L can significantly reduce MACBAR of sevoflurane by 48％ and 63％ respectively in gynecological patients undergoing laparoscopic surgery. However, the value of catecholamineBAR was not influenced by the changes of remifentanil's target plasma concentration and the end-tidal sevoflurane concentration. Key words: Sevoflurane; Remifentanil; MAC ; Adrenergic response; Catecholamine; Pneumoperitoneum

Effects of different doses of dexmedetomidine on MACBAR of sevoflurane in patients undergoing lower abdominal surgery

Objective To investigate the effects of different doses of dexmedetomidine on the minimum alveolar concentration of sevoflurane for blunting responses to skin incision ( MACBAR ) in patients undergoing lower abdominal surgery. Methods Sixty ASA Ⅰ or Ⅱ patients, aged 25-55 yr, weighing 45-75 kg, undergoing electire lower abdominal surgery under general anesthesia, were randomly divided into 4 groups ( n = 15 each): control group (Do group) and 3 dexmedetomidine groups (D1, D2 and D3 groups). The patients were unpremedicated.Dexmedetomidine was not used in group D0. A loading dose of dexmedetomidine 0.1μg/kg was injected iv over 10 min, and then dexmedetomidine was infused at a rate of 0.4, 0.8 and 1.2 μg· kg- 1 · h - 1 for 30 min in groups D1-3 respectively. Anesthesia was induced with inhalation of 8 % sevoflurane. Laryngeal mask airway was inserted when BIS value decreased to 45-55. The patients were mechanically ventilated with inhalation of sevoflurane and a mixture of 50% nitrous oxide and 50% oxygen, and the fresh gas flow was set at 1 L/min. In D0-3 groups, the initial end-tidal concentrations of sevoflurane were 3.0%, 2.5%, 2.0% and 1.5% respectively. The patients' response to skin incision was described as effective if MR or MAP increased by ＜ 15%, or ineffective (MR or MAP increased by ≥ 15%). When the response was effective, the end-tidal concentration of sevoflurane was decreased in the next patient, when ineffective, increased, and the ratio between the two successive concentrations was 0.9.The MRCBAR of sevoflurane was determined by up-and-down method, and 95% confidence interval was calculated.Results The MRCBAR (95% confidence interval) of sevoflurane was 2.85% (2.44%-3.32%), 1.91%(1.61%-2.26%), 1.52% (1.31%-1.77%), and 1.34% (1.15%-1.57%)in D0-3 groups respectively. The MRCBAR of sevoflurane was significantly lower in D1-3 groups than in D0 group, and in D2 and D3 groups than in group D1 (P ＜0.05＝. There was no significant difference in MRCBAR of sevoflurane between D2 and D3 groups (P ＞0.05) .Conclusion Continuous infusion of dexmedetomidine at 0.4, 0.8 and 1.2 μg·kg-1 ·h-1 for 30 min results in a decrease in MACBAR of sevoflurane and enhances the inhibitory effect of sevoflurane on the stress response, and in a dose-dependent manner. Key words: Dexmedetomidine; Dose-response relationship,drug; Stress; Sevoflurane

Extrapolation and interpretation

EDITOR: We would like to congratulate Albertin and colleagues on their study into the effects of adding nitrous oxide on the MACBAR of sevoflurane given with two target-controlled concentrations of remifentanil in women [1]. They used a modified up-down sequential allocation technique to determine the MACBAR of sevoflurane, described initially by Jung and Choi [2]. This involved two stages. The first used a standard up-down sequence using predetermined equally spaced test levels until three reversals were observed. For the second stage, the testing interval was reduced, restarting the up-down sequence at the nearest level to the average and continuing for four reversals. The logic is that by reducing the testing interval, the value of the final estimator is more precise and the doses used in the second stage are closer to the true median dose. A number of issues follow. The methods, as described in this paper, do not appear to have been followed consistently in that authors appear to have broken their own rule of achieving three reversals prior to moving on to the second stage of the sequential allocation technique in Figures 2 and 4. Figures 1 and 3, although more in keeping with the stated design, show considerable variability and limited stability in the first stage. They also present estimates of ED95 (should be EC95 for sevoflurane concentration), which are extrapolated well beyond the limits of the data as presented. Such extrapolations are better suited to discussion rather than results. They also report similar estimates of precision for EC50 and EC95, where the latter is usually more imprecise. Also, incidentally Figure 4 appears to have an error in the correct plotting of the MACBAR and error bar. The main issue, however, is how to best present and analyse these data given that the method described by the authors removes up to approximately 60% of the subjects from the analysis. The question is whether we can simply ‘ignore’ the initial data? Intuitively the answer is ‘yes’ for Figures 2 and 4, but perhaps ‘no’ for Figures 1 and 3. Also whilst the simulations by Jung [2] show the expected reductions in mean square error by reducing the testing interval, it is not clear what should be done about the variability of data with larger testing intervals where this is trending or when the reversals are unbalanced as in this study. (The schematic in the Jung paper [2] showed a balanced example). A logical approach is then to consider all the data together. Whilst this will decrease the precision of the estimates, it implies that we are not discarding the variability of otherwise valid observations. The authors present an up-down analysis and correctly use logistic regression as a back-up analysis. In this instance, Table 1 shows the logistic regression results reported in the study and an additional analysis of all the data using a loglogistic maximum likelihood approach. They confirm the highly significant (P = 0.001) effects of nitrous oxide and alfentanil on MACBAR of sevoflurane. However, the fiducial 95% confidence intervals (CI) for the estimates of ED95 are relatively imprecise compared to the original report.Table 1: Original results with 95% CI for EC95.In conclusion, again the authors are to be commended on using a dose-varying methodology. Care must be taken when using regression methods to extrapolate point estimates beyond the data as collected and should not be assigned the same weight as median estimates. M. O. Columb P. Tandon Acute Intensive Care Unit, South Manchester University Hospital, Wythenshawe, Manchester, UK

Questioning the cardiocirculatory excitatory effects of opioids under volatile anaesthesia

Opioid-induced hyperalgesia has been demonstrated in awake animals. We observed an increased haemodynamic reactivity in response to noxious stimuli in rats under sevoflurane anaesthesia treated with a very low dose of sufentanil. The aim of this investigation was to determine whether the two phenomena share a common origin: an opioid-induced excitatory reaction. To address this, we administered several drugs with proven efficacy in opioid hyperalgesia to rats presenting with haemodynamic hyper-reactivity. The MACbar of sevoflurane was measured in controls and in animals treated with sufentanil 0.005 micro g kg(-1) min(-1) before and after administration of i.v. (0.25, 0.5 mg kg(-1)) and intrathecal (i.t.) (250 micro g) ketamine, i.v. (0.5, 1 mg kg(-1)) and i.t. (30 micro g) MK-801(NMDA antagonist), i.v. (0.1, 0.5 mg kg(-1)) naloxone, i.v. (10 mg kg(-1)) and i.t. (50, 100 micro g) ketorolac or i.t. (100, 150 micro g) meloxicam (COX-2 inhibitor). Sufentanil 0.005 micro g kg(-1) min(-1) significantly increased MACbar (3.2 (sd 0.3) versus 1.9 (0.3) vol%). With the exception of naloxone, all drugs displayed a significant MACbar-sparing effect (>50%) in controls. Naloxone completely prevented haemodynamic hyperactivity. Two patterns of reaction were recorded for the other drugs: either hyper-reactivity was suppressed and the MACbar-sparing effect was maintained (i.t. ketamine, i.t. MK-801, i.t. ketorolac [100 micro g], i.t. meloxicam [150 micro g]) or hyper-reactivity was blocked but MACbar-sparing effect was lost (i.v. ketamine [0.5 mg kg(-1)], i.v. MK-801 [0.5, 1 mg kg(-1)], i.v. ketorolac [10 micro g kg(-1)], i.t. ketorolac [50 micro g], i.t. meloxicam [100 micro g]). We have demonstrated that low-dose sufentanil-induced haemodynamic hyper-reactivity is an excitatory micro -opiate-related phenomenon. This effect is reversed by drugs effective in treating opiate-induced hyperalgesia.

Fentanyl augments block of sympathetic responses to skin incision during sevoflurane anaesthesia in children

We studied 61 healthy ASA 1 patients (aged 2-6 yr) to determine if fentanyl affects the minimum alveolar concentration which blocks adrenergic responses to skin incision (MAC-BAR) in 50% of children in the presence of 60% nitrous oxide. Patients were allocated randomly to one of three fentanyl groups to receive 0, 2 or 4 micrograms kg-1. Patients also received sevoflurane at a preselected end-tidal concentration according to an 'up-and-down' design. After a steady-state sevoflurane concentration had been maintained for at least 15 min, fentanyl was given i.v. Skin incision was performed 5 min after administration of fentanyl. The response was considered positive if heart rate (HR) or mean arterial pressure (MAP) increased by 15% or more. The MAC-BAR of sevoflurane was 1.45 MAC (95% confidence intervals 1.25-1.65 MAC), and this was reduced markedly to 0.63 MAC and 0.38 MAC by addition of fentanyl 2 and 4 micrograms kg-1, respectively. A ceiling effect was not observed and there was a significant difference between the 2 and 4 micrograms kg-1 groups.