Hernán R. Muñoz

Nitrous oxide (N2O) reduces postoperative opioid-induced hyperalgesia after remifentanil–propofol anaesthesia in humans

BACKGROUND The aim of this study was to test if intraoperative administration of N(2)O during propofol-remifentanil anaesthesia prevented the onset of postoperative opioid-induced hyperalgesia (OIH). METHODS Fifty adult ASA I-II patients undergoing elective open septorhinoplasty under general anaesthesia were studied. Anaesthesia was with propofol, adjusted to bispectral index (40-50), and remifentanil (0.30 μg kg(-1) min(-1)). Patients were assigned to one of the two groups: with N(2)O (70%) and without N(2)O (100% oxygen). Mechanical pain thresholds were measured before surgery and 2 and 12-18 h after surgery. Pain measurements were performed on the arm using hand-held von Frey filaments. A non-parametric analysis of variance was used in the von Frey data analysis. P<0.05 was considered statistically significant. RESULTS Baseline pain thresholds to mechanical stimuli were similar in both groups, with mean values of 69 [95% confidence interval (CI): 50.2, 95.1] g in the group without N(2)O and 71 (95% CI: 45.7, 112.1) g in the group with N(2)O. Postoperative pain scores and cumulative morphine consumption were similar between the groups. The analysis revealed a decrease in the threshold value in both groups. However, post hoc comparisons showed that at 12-18 h after surgery, the decrease in mechanical threshold was greater in the group without N(2)O than the group with N(2)O (post hoc analysis with Bonferronis correction, P<0.05). CONCLUSIONS Intraoperative 70% N(2)O administration significantly reduced postoperative OIH in patients receiving propofol-remifentanil anaesthesia.

Dexamethasone for postoperative nausea and vomiting prophylaxis: effect on glycaemia in obese patients with impaired glucose tolerance.

Background and objective Dexamethasone given to prevent postoperative nausea and vomiting may produce significant hyperglycaemia in the perioperative period. The effect of dexamethasone on patients with impaired glucose tolerance is unknown. Methods Thirty obese patients with impaired glucose tolerance undergoing laparoscopic Roux-en-Y gastric bypass surgery were studied in a double-blind fashion. Patients were randomly distributed into two groups: the dexamethasone group (n = 15) received dexamethasone 8 mg intravenously after induction of anaesthesia; the control group (n = 15) received isotonic saline. Fingerprick capillary blood glucose concentrations were measured at baseline and every 2 h during the first 12 h after the start of surgery. Results In both groups, all blood glucose concentrations measured after the beginning of surgery were higher than baseline values. However, the dexamethasone group showed higher glucose concentrations than the control group from the 6th to the 12th hour of the study. In addition, the maximum blood glucose value in the dexamethasone group (10.4 ± 1.6 mmol l−1) was higher than in the controls (8.8 ± 1.7 mmol l−1) (P < 0.05). Conclusion Dexamethasone, 8 mg, intravenously administered at the beginning of laparoscopic bariatric surgery in patients with impaired glucose tolerance is associated with significantly increased postoperative blood glucose concentrations.

Effect site concentrations of propofol producing hypnosis in children and adults: comparison using the bispectral index.

Background:  No study has determined the concentration of propofol producing a degree of hypnosis compatible with anaesthesia in children. As a result, concentrations determined in adults are recommended for children. As this can result in an inadequate depth of anaesthesia, we determined the predicted effect site concentration (Ce) of propofol necessary to obtain a bispectral index (BIS) of 50 in 50% (ECe50) of children and adults.

The Influence of Age on the Dynamic Relationship Between End-Tidal Sevoflurane Concentrations and Bispectral Index

BACKGROUND: Age is an important determinant of the pharmacokinetic profile of inhaled anesthetics. The influence of age on the dynamic profile of sevoflurane’s effect has not been well described. We performed this study to characterize the influence of age and other covariates on the dynamic relationship between sevoflurane end-tidal concentration (CET) and its effect measured by bispectral index (BIS). METHODS: Fifty patients, aged 3–71 yr, scheduled for minor surgery were prospectively studied. The BIS and sevoflurane CET were continuously measured during the study period. During maintenance of anesthesia and after stable BIS values of 60–65 were obtained, the inspired concentration of sevoflurane was increased to 5 vol % for 5 min or until BIS <40 and then decreased. The dynamic relationship between sevoflurane CET and its effect as measured by BIS during this transition period were modeled with an inhibitory Emax model using a population pharmacokinetic–pharmacodynamic approach with NONMEM V. A predictive check method was used to validate the final model. RESULTS: The sensitivity to sevoflurane’s effect as measured by BIS expressed in the C50 [steady-state CET eliciting half of maximum response (Imax)] increased with age. The speed of change of sevoflurane’s effect, expressed as the effect–site equilibration half-life (t1/2 ke0), increased at older ages. The predictive check analysis confirmed the adequacy of the model. CONCLUSIONS: Age significantly affects the dynamic relationship between sevoflurane CET and its effect measured with BIS.

Evaluation of the effect of intravenous lidocaine on propofol requirements during total intravenous anaesthesia as measured by bispectral index

BACKGROUND I.V. lidocaine is increasingly used as an adjuvant during general anaesthesia. The aim of this study was to evaluate the effect of i.v. lidocaine in reducing propofol anaesthetic requirements during total i.v. anaesthesia (TIVA) maintenance and to evaluate its effect on early recovery from anaesthesia. METHODS Forty adult patients undergoing elective laparoscopic cholecystectomy under TIVA were randomly allocated into the lidocaine group (administered 1.5 mg kg(-1) i.v. lidocaine over 5 min followed by 2 mg kg(-1) h(-1)) and the control group (administered an equal volume of saline). Propofol was administered using a target-controlled infusion to maintain the bispectral index values between 40 and 60. After surgery, all infusions were discontinued and the time to extubation was recorded. Serial arterial blood samples were drawn to assess drug plasma levels. RESULTS The maintenance dose of propofol was significantly lower in the lidocaine group [6.00 (0.97) mg kg(-1) h(-1)] vs the control group [7.25 (1.13) mg kg(-1) h(-1); P=0.01]. Propofol plasma levels measured at the end of the infusion were 3.71 (0.89) μg ml(-1) in the lidocaine group and 3.67 (1.28) μg ml(-1) in the control group (P=0.91). The median time to extubation was longer (11.0 min; range: 10.0-21.0) in the lidocaine group vs the control group (8.3 min; range: 5.5-12.5; P=0.02). CONCLUSIONS I.V. lidocaine reduces propofol requirements during the maintenance phase of TIVA, particularly during surgical stimulation. This sparing effect is associated with an increased time to extubation. Owing to its effect on early recovery from anaesthesia, i.v. lidocaine should be taken into account when used as a component of i.v. anaesthesia.

The effect of nitrous oxide on jugular bulb oxygen saturation during remifentanil plus target-controlled infusion propofol or sevoflurane in patients with brain tumors.

During propofol/fentanyl anesthesia, a large percentage of patients have jugular bulb oxygen saturation (Sjo2) <50%. The incidence is less with isoflurane/N2O. We evaluated the effect of N2O on Sjo2 during remifentanil-based anesthesia with concurrent propofol or sevoflurane in 20 adults undergoing brain tumor surgery. Anesthesia was randomized: Group 1 (n = 10), target-controlled infusion propofol; and Group 2 (n = 10), thiopental 2–3 mg/kg followed by sevoflurane 0.9% end-tidal. Jugular bulb and arterial blood samples for gas analysis were withdrawn during the administration of oxygen 33% with nitrogen 67% and then with N2O 67%. All samples were drawn before surgery and 20 min after the addition of the study gas and with an ETco2 26–28 mm Hg and mean arterial pressure >90 mm Hg. Both groups had similar demographic and physiologic data. In the Propofol group, Sjo2 was 50% ± 10% with nitrogen and 52% ± 9% with N2O (not significant); in the Sevoflurane group, however, N2O 67% increased Sjo2 from 56% ± 13% to 66% ± 12% (P < 0.01). This indicates that N2O does not reduce the incidence of low Sjo2 values during propofol anesthesia.

Effect of intravenous fluid therapy on postoperative vomiting in children undergoing tonsillectomy

BACKGROUND Postoperative vomiting (POV) is one of the most frequent complications of tonsillectomy in children. The aim of this study was to evaluate the antiemetic effect of super-hydration with lactated Ringers solution in children undergoing elective otorhinolaryngological surgery. METHODS One hundred ASA I-II children, aged 1-12 yr, undergoing elective tonsillectomy, with or without adenoidectomy, under general anaesthesia were studied. Induction and maintenance of anaesthesia were standardized with fentanyl, mivacurium, and sevoflurane in N(2)O/O(2). Subjects were assigned to one of the two groups: 10 ml kg(-1) h(-1) lactated Ringers solution or 30 ml kg(-1) h(-1) lactated Ringers solution. A multivariable logistic regression was used for assessing the effects of super-hydration on POV (defined as the presence of retching, vomiting, or both). A value of P<0.05 was considered statistically significant. RESULTS During the first 24 h postoperative, the incidence of POV decreased from 82% to 62% (relative reduction of 24%, P=0.026). In the adjusted logistic regression model, subjects in the 10 ml kg(-1) h(-1) group had an odds ratio of POV that was 2.92 (95% confidence interval: 1.14, 7.51) for POV compared with subjects in the 30 ml kg(-1) h(-1) group. CONCLUSIONS Intraoperative administration of 30 ml kg(-1) h(-1) lactated Ringers solution significantly reduced the incidence of POV during the first 24 h postoperative. Our results support the use of super-hydration during tonsillectomy, as an alternative way to decrease the risk of POV in children.

The Dynamic Relationship Between End-Tidal Sevoflurane Concentrations, Bispectral Index, and Cerebral State Index in Children

BACKGROUND: To guide anesthetic administration with electroencephalogram monitors in children, an adequate characterization of the anesthetic effect measured by these monitors in this population is needed. We sought to quantify and compare the dynamic profile of sevoflurane’s effect measured with the cerebral state index (CSI) and the bispectral index (BIS) in children. METHODS: Fifteen healthy children, aged 3–15 yr, scheduled to undergo minor surgery were prospectively studied. During the simultaneous recording of CSI and BIS, the sevoflurane vaporizer was set at 6 vol % for 5 min and then decreased. End-tidal concentrations (CET) were measured. The CET–sevoflurane effect–site concentration equilibration and pharmacodynamics were modeled. Goodness of fit between models was compared. Data are typical value (coefficient of variation). RESULTS: Within the anesthetic depth range studied, the rate of change of sevoflurane’s effect expressed as the effect–site equilibration half-life (t1/2 ke0) was slower with the CSI [2.0 (14) min] than with BIS [1.2 (53) min] (P < 0.05). The estimated baseline effect of BIS and CSI before sevoflurane administration (E0) was 84 (39) for CSI and 87 (7) for BIS (NS). The sensitivity to sevoflurane hypnotic effect expressed in the C50 [steady-state CET eliciting half of the maximum response (Emax)] was 2.1 (68) % with CSI and 2.1 (16)% with BIS (NS). The Emax with CSI 45 (0) was higher than that with BIS 27 (39) (P < 0.05). The population prediction error was significantly better for BIS (−0.7 ± 26.9) than for CSI (−3.0 ± 178.6) (P < 0.05). CONCLUSIONS: In children, the t1/2 ke0 of sevoflurane and the pharmacodynamics of sevoflurane were quantified and the results were entirely dependent on the monitor used to measure its hypnotic effect. Within the anesthetic depth range studied, the rate of change of sevoflurane’s effect was slower with the CSI. To adequately guide sevoflurane administration with these monitors in children, these differences should be considered.

Prospective evaluation of the time to peak effect of propofol to target the effect site in children.

Background: The plasma‐effect site equilibration rate constant (ke0) of propofol has been determined in children with the use of the time to maximum effect (tpeak), however, it has not been validated. The objective was to measure the tpeak; of propofol with two depths of anesthesia monitors in children and to evaluate these measurements with a target‐controlled infusion (TCI) system.

Target-controlled infusion of remifentanil or fentanyl during extra-corporeal shock-wave lithotripsy

Background and objective: Target‐controlled infusions (TCIs) of remifentanil and fentanyl in conscious sedation regimes for extra‐corporeal shock‐wave lithotripsy have not been reported. We estimated the effect site concentrations of remifentanil and fentanyl needed to obtain adequate analgesia in 50% of patients (EC50) and compared both drugs in terms of intra‐ and post‐procedure complications. Methods: Forty‐four adult patients were randomly distributed into two groups: Group R received remifentanil and Group F received fentanyl TCI with initial effect site concentrations of 1.5 and 2 ng mL−1, respectively. Pain was assessed using a 10‐point verbal analogue scale and <3 was considered adequate analgesia. Increments or decrements of 0.5 ng mL−1 were then introduced for subsequent patients according to Dixons up and down method. During the rest of the procedure, TCI was adjusted to maintain verbal analogue scale <3. Results: Remifentanil and fentanyl EC50 were 2.8 ng mL−1 (95% confidence interval (CI): 1.8‐3.7 ng mL−1) and 2.9 ng mL−1 (95% CI: 1.7‐4.1 ng mL−1), respectively (n.s.). At EC50, the probability of having a respiratory rate <10 was 4% (95% CI: 0‐57%) for remifentanil and 56% (95% CI: 13‐92%) for fentanyl. Hypoxaemia, vomiting and sedation were more frequent in Group F during and after the procedure (P < 0.05). Conclusions: A similar EC50 but more respiratory depression, sedation and PONV were found with fentanyl TCI than with remifentanil TCI.