Predicted effect-site concentrations of remimazolam for i-gel insertion: a prospective randomized controlled study.

This study is the first to report 50% and 95% effect-site concentrations (EC50 and EC95, respectively) of the new short-acting benzodiazepine, remimazolam, for the successful insertion of i-gels with co-administration of fentanyl. Thirty patients (38 ± 5 years old, male/female = 4/26) were randomly assigned into five groups to receive one of five different remimazolam doses (0.1, 0.15, 0.2, 0.25, and 0.3 mg/kg bolus followed by infusion of 1, 1.5, 2, 2.5, and 3 mg/kg/h, respectively, for 10 min), which were designed to maintain a constant effect-site concentration of remimazolam at the time of i-gel insertion. At 6 min after the start of remimazolam infusion, all patients received 2 µg/kg fentanyl. i-gel insertion was attempted at 10 min and the success or failure of insertion were assessed by the patient response. Probit analysis was used to estimate the EC50 and EC95 values of remimazolam with 95% confidence intervals (CIs). In the five remimazolam dose groups, two, two, four, five, and six of the six patients in each group had an i-gel successfully inserted. Two patients in the lowest remimazolam dose group were conscious at the time of i-gel insertion and were counted as failures. The EC50 and EC95 values of remimazolam were 0.88 (95% CI, 0.65-1.11) and 1.57 (95% CI, 1.09-2.05) µg/ml, respectively. An effect-site concentration of ≥ 1.57 µg/ml was needed to insert an i-gel using remimazolam anesthesia, even with 2 µg/kg fentanyl. Trial registration: The study was registered in Japan Registry of Clinical Trials on 19 April 2021, Code jRCTs041210009.

IMPACT OF HIGH-DOSE VASOPRESSOR DURING ENDOTOXIC SHOCK ON THE CEREBRAL, LINGUAL, HEPATIC, AND RENAL MICROCIRCULATION EVALUATED BY NEAR-INFRARED SPECTROSCOPY IN SWINE.

ABSTRACT: Background: High-dose vasopressors maintain blood pressure during septic shock but may adversely reduce microcirculation in vital organs. We assessed the effect of high-dose norepinephrine and vasopressin on the microcirculation of the brain, tongue, liver, and kidney during endotoxic shock using near-infrared spectroscopy (NIRS). Methods: Thirteen pigs (24.5 ± 1.8 kg) were anesthetized, and an NIRS probe was attached directly to each organ. Approximately 0.2, 0.5, 1, and 2 µg/kg/min of norepinephrine were administered in a stepwise manner, followed by 0.5, 1, 2, and 5 µg/kg/min of sodium nitroprusside in normal condition. Moreover, 1 µg/kg/h of lipopolysaccharide was administered continuously after 100 µg bolus to create endotoxic shock and after 1,000 mL of crystalloid infusion and high-dose norepinephrine (2, 5, 10, and 20 µg/kg/min) and vasopressin (0.6, 1.5, 3, and 6 U/min) were administered in a stepwise manner. The relationship between the MAP and each tissue oxygenation index (TOI) during vasopressor infusion was evaluated. Results: Three pigs died after receiving lipopolysaccharides, and 10 were analyzed. An increase of >20% from the baseline MAP induced by high-dose norepinephrine during endotoxic shock reduced the TOI in all organs except the liver. The elevation of MAP to baseline with vasopressin alone increased the kidney and liver TOIs and decreased the tongue TOI. Conclusion: Forced blood pressure elevation with high-dose norepinephrine during endotoxic shock decreased the microcirculation of vital organs, especially the kidney. Cerebral TOI may be useful for identifying the upper limit of blood pressure, at which norepinephrine impairs microcirculation.

Effects of volatile anesthetics on circadian rhythm in mice: a comparative study of sevoflurane, desflurane, and isoflurane.

PURPOSE: Volatile anesthetics affect the circadian rhythm of mammals, although the effects of different types of anesthetics are unclear. Here, we anesthetized mice using several volatile anesthetics at two different times during the day. Our objective was to compare the effects of these anesthetics on circadian rhythm. METHODS: Male adult C57BL/6 J mice were divided into eight groups (n = 8 each) based on the anesthetic (sevoflurane, desflurane, isoflurane, or no anesthesia) and anesthesia time (Zeitgeber time [ZT] 6-12 or ZT18-24). Mice were anesthetized for 6 h using a 0.5 minimum alveolar concentration (MAC) dose under constant dark conditions. The difference between the start of the active phase before and after anesthesia was measured as a phase shift. Clock genes were measured by polymerase chain reaction in suprachiasmatic nucleus (SCN) samples removed from mouse brain after anesthesia (n = 8-9 each). RESULTS: Phase shift after anesthesia at ZT6-12 using sevoflurane (- 0.49 h) was smaller compared with desflurane (- 1.1 h) and isoflurane (- 1.4 h) (p < 0.05). Clock mRNA (ZT6-12, p < 0.05) and Per2 mRNA (ZT18-24, p < 0.05) expression were different between the groups after anesthesia. CONCLUSION: 0.5 MAC sevoflurane anesthesia administered during the late inactive to early active phase has less impact on the phase shift of circadian rhythm than desflurane and isoflurane. This may be due to differences in the effects of volatile anesthetics on the expression of clock genes in the SCN, the master clock of the circadian rhythm.

Stomach, liver, kidney and skeletal muscle autoregulation evaluated by near-infrared spectroscopy in a swine model.

PURPOSE: Different organs have different autoregulatory capacities for blood pressure changes and/or circulatory volume changes. This study assessed the autoregulation of the stomach, liver, kidney and skeletal muscle, under baseline, hypovolemic, and post-fluid-resuscitation conditions using near-infrared spectroscopy (NIRS). METHODS: Ten pigs (bodyweight 24.5 ± 0.5 kg) were anesthetized with 2.5% isoflurane and administered 0.5, 1, 2 and 5 µg kg- 1 min- 1 of phenylephrine at 10-min intervals, followed by similar stepwise infusion of sodium nitroprusside (SNP) to induce a wide range of mean arterial pressures (MAPs). A 600-ml bleed was induced to create the hypovolemic condition, and only phenylephrine was re-administered. Hydroxyethyl starch (600 ml) was infused to create the post-fluid-resuscitation condition, and phenylephrine and SNP were re-administered. Average relationships between mean arterial pressure (MAP) and each tissue oxygenation index (TOI) were assessed, and the individual relationships were evaluated based on the correlation coefficients between MAP and TOI during each vasoactive drug infusion. RESULTS: Based on the evaluation using each TOI as a substitute of blood flow, the kidney autoregulation was robust, similar to muscle, but had a prominent lower limit. The stomach had weaker autoregulation than the kidney and muscle. The liver had no autoregulation. The kidney TOI showed 2-fold greater changes in response to volume condition changes than the stomach and liver TOIs. CONCLUSION: In our NIRS-based assessment of autoregulatory capacity, the liver oxygenation is highly blood pressure dependent, and the kidney is highly susceptible and the skeletal muscle is highly tolerable to low blood pressure and volume loss.

Association between remimazolam and postoperative delirium in older adults undergoing elective cardiovascular surgery: a prospective cohort study.

PURPOSE: Postoperative delirium is one of the most common complications after cardiovascular surgery in older adults. Benzodiazepines are a reported risk factor for delirium; however, there are no studies investigating remimazolam, a novel anesthetic agent. Therefore, we prospectively investigated the effect of remimazolam on postoperative delirium. METHODS: We included elective cardiovascular surgery patients aged ≥ 65 years at Hamamatsu University Hospital between August 2020 and February 2022. Patients who received general anesthesia with remimazolam were compared with those who received other anesthetics (control group). The primary outcome was delirium within 5 days after surgery. Secondary outcomes were delirium during intensive care unit stay and hospitalization, total duration of delirium, subsyndromal delirium, and differences in the Mini-Mental State Examination scores from preoperative to postoperative days 2 and 5. To adjust for differences in the groups' baseline covariates, we used stabilized inverse probability weighting as the primary analysis and propensity score matching as the sensitivity analysis. RESULTS: We enrolled 200 patients; 78 in the remimazolam group and 122 in the control group. After stabilized inverse probability weighting, 30.3% of the remimazolam group patients and 26.6% of the control group patients developed delirium within 5 days (risk difference, 3.8%; 95% confidence interval -11.5% to 19.1%; p = 0.63). The secondary outcomes did not differ significantly between the groups, and the sensitivity analysis results were similar to those for the primary analysis. CONCLUSION: Remimazolam was not significantly associated with postoperative delirium when compared with other anesthetic agents.

Recall of extubation after remimazolam anesthesia with flumazenil antagonism during emergence: a retrospective clinical study.

PURPOSE: This study was performed to examine and compare the incidence of extubation recall in surgical patients who underwent remimazolam anesthesia with flumazenil antagonism during emergence and in those who underwent propofol anesthesia. METHODS: One hundred sixty-three patients who underwent surgery using general endotracheal or supraglottic airway anesthesia with propofol (n = 97) or remimazolam (n = 66) were retrospectively analyzed. Remimazolam was antagonized by flumazenil after discontinuation of remimazolam at the end of surgery. The endotracheal tube or supraglottic airway was removed after surgery was complete, and consciousness and adequate spontaneous breathing were confirmed. The incidence of extubation recall was compared between the remimazolam and propofol anesthesia groups using propensity score matching. RESULTS: Extubation recall was observed in 28 patients (17%). After propensity score matching, the incidence of extubation recall did not significantly differ between the remimazolam and propofol anesthesia groups (15.6% vs. 18.8%; p = 1.000). CONCLUSION: The incidence of extubation recall after remimazolam anesthesia with flumazenil antagonism during emergence did not significantly differ from that after propofol anesthesia.

Influence of hemorrhage and subsequent fluid resuscitation on transcranial motor-evoked potentials under desflurane anesthesia in a swine model.

PURPOSE: Hemorrhage increases the effect of propofol and could contribute to false-positive transcranial motor-evoked potential (TcMEP) responses under total intravenous anesthesia (TIVA). We investigated the influence of hemorrhage and subsequent fluid resuscitation on TcMEPs under desflurane anesthesia. METHODS: Sixteen swine (25.4 ± 0.4 kg) were anesthetized with a 4% end-tidal desflurane concentration (EtDes), which was incrementally increased to 6%, 8%, and 10% and then returned to 4% every 15 min. This procedure was repeated twice (baseline). After baseline measurements, animals were allocated to either the hemorrhage (n = 12) or control (n = 4) group. In the hemorrhage group, 600 ml of blood was removed and the EtDes protocol described above was applied. Hypovolemia was resuscitated using 600 ml of hydroxyethyl starch and the EtDes protocol was applied again. TcMEPs were measured at each EtDes. In the control group, measurements were performed without hemorrhage or fluid infusion. RESULTS: TcMEP responses were observed in all conditions in all limbs with 4% EtDes (0.4 MAC). TcMEP amplitudes decreased according to the EtDes to a greater degree in the lower limbs compared with the upper limbs. Hemorrhage enhanced the effect of desflurane on TcMEP amplitudes, and decreased TcMEP by 41 ± 12% in upper limbs and 63 ± 17% in lower limbs compared with baseline. Subsequent fluid resuscitation did not reverse TcMEP amplitudes. CONCLUSIONS: TcMEP amplitudes decrease during hemorrhage under desflurane anesthesia. This phenomenon might result from an enhanced effect of desflurane on the spinal motor pathway without increasing the desflurane concentration.

Assessment of the benefits of head-up preoxygenation using near-infrared spectroscopy with pulse oximetry in a swine model.

Compared with supine positioning, head-up positioning improves preoxygenation and prolongs the time to oxygen desaturation. We reevaluated benefits of head-up positioning using near-infrared spectroscopy (NIRS) with pulse oximetry in a pig model. Six pigs (mean ± SD weight: 25.3 ± 0.6 kg) were anesthetized with isoflurane and evaluated in four positions-supine, head-up, head-down, head-up to supine-just before apnea (positions' order after "supine" was randomized). In each position, after 5 min of preoxygenation with 100% oxygen, apnea was induced and the time to SpO2 < 70% measured. Hemodynamic and blood-gas variables and the cerebral tissue oxygenation index (TOI) were evaluated using NIRS and recorded. Hypovolemia was induced by collecting 600 mL blood. Apnea experiment was performed again in each position. The times (seconds) ± SD to SpO2 < 70% were 108 ± 13 (supine), 138 ± 15 (head-up; P < 0.0001 vs all other positions); 101 ± 12 (head-down) and 106 ± 15 (head-up to supine) during normovolemia, and 110 ± 29, 120 ± 7 (not significant vs all other positions), 101 ± 16, and 106 ± 11, respectively, during hypovolemia. Although the TOI was not associated with the positions during normovolemia, the head-up position during hypovolemia decreased TOI from 62% ± 6% (supine) to 50% ± 9% (head-up; P = 0.0019) before preoxygenation, and it remained low during apnea. The head-up position improves preoxygenation, but repositioning to supine negates the benefits. Head-up positioning during evident hypovolemia should be avoided because the cerebral oxygenation could decrease.

Desflurane anesthesia shifts the circadian rhythm phase depending on the time of day of anesthesia.

Desflurane is one of the most frequently used inhalational anesthetics in clinical practice. A circadian rhythm phase-shift after general anesthesia with sevoflurane or isoflurane has been reported in mice, but few studies have reported this effect with desflurane. In the present study, we examined the rest/activity rhythm of mice by counting the number of running wheel rotations, and we found that desflurane anesthesia caused a phase shift in the circadian rhythm that was dependent on the time of day of anesthesia. We also found that desflurane anesthesia altered the relative mRNA expression of four major clock genes (Per2, Bmal, Clock, and Cry1) in the suprachiasmatic nucleus (SCN). These results are important for elucidating the effects of desflurane on the SCN, which is the master clock for the mammalian circadian rhythm. Further studies on the relationship between anesthesia and circadian rhythm may lead to the prevention and treatment of postoperative complications related to circadian rhythms.

Spinal cord autoregulation using near-infrared spectroscopy under normal, hypovolemic, and post-fluid resuscitation conditions in a swine model: a comparison with cerebral autoregulation.

BACKGROUND: Few studies have investigated spinal cord autoregulation using near-infrared spectroscopy (NIRS). Here, we assessed spinal cord autoregulation under normal, hypovolemic, and post-fluid resuscitation conditions compared with cerebral autoregulation. METHODS: Ten pigs (36.1 ± 1.1 kg) were anesthetized with 2.5% isoflurane, before phenylephrine administration at 0.5, 1, 2, and 5 µg kg-1 min-1 in a stepwise fashion at 10-min intervals (baseline), followed by similar administration of sodium nitroprusside (SNP). Hypovolemia was induced by a 600-ml bleed (25% estimated total blood volume). Only phenylephrine was readministered (same protocol). Hypovolemia was reversed by infusing 600 ml hydroxyethyl starch, before readministering phenylephrine and SNP. The relationships between mean arterial pressure (MAP) and cerebral, thoracic, and lumbar spinal cord tissue oxygenation indices (TOIs) were evaluated. RESULTS: Thoracic and lumbar spinal cord TOIs were approximately 15% and 10% lower, respectively, than the cerebral TOI at similar MAPs. The average relationship between MAP and each TOI showed an autoregulatory pattern, but negative correlations were observed in the cerebral TOI during phenylephrine infusion. A 600-ml bleed lowered each relationship < 5% and subsequent fluid resuscitation did not change the relationship. Individual oxygenation responses to blood pressure indicated that the spinal cord is more pressure-passive than the cerebrum. Paradoxical responses (an inverse relationship of tissue oxygenation to MAP) were observed particularly in cerebrum during phenylephrine infusion and were rare in the spinal cord. CONCLUSIONS: Spinal cord autoregulation is less robust than cerebral autoregulation and more pressure-dependent. Similar to cerebral oxygenation, spinal cord oxygenation is volume-tolerant but is more sensitive to hypotension.

1.2% Hydrogen gas inhalation protects the endothelial glycocalyx during hemorrhagic shock: a prospective laboratory study in rats.

PURPOSE: Hydrogen gas (H2) inhalation improved the survival rate of hemorrhagic shock. However, its mechanisms are unknown. We hypothesized that H2 protected the endothelial glycocalyx during hemorrhagic shock and prolonged survival time. METHODS: 83 Sprague-Dawley rats were anesthetized with isoflurane. The animals were randomly assigned to 5 groups: room air with no shock, 1.2% H2 with no shock, room air with shock (Control-S), 1.2% H2 with shock (H21.2%-S), and 3.0% H2 with shock (H23.0%-S). Shock groups were bled to a mean arterial pressure of 30-35 mmHg and held for 60 min, then resuscitated with normal saline at fourfold the amount of the shed blood volume. RESULTS: The syndecan-1 level was significantly lower in the H21.2%-S [8.3 ± 6.6 ng/ml; P = 0.01; 95% confidence interval (CI), 3.2-35.8] than in the Control-S (27.9 ± 17.0 ng/ml). The endothelial glycocalyx was significantly thicker in the H21.2%-S (0.15 ± 0.02 µm; P = 0.007; 95% CI, 0.02-0.2) than in the Control-S (0.06 ± 0.02 µm). The survival time was longer in the H21.2%-S (327 ± 67 min, P = 0.0160) than in the Control-S (246 ± 69 min). The hemoglobin level was significantly lower in the H21.2%-S (9.4 ± 0.5 g/dl; P = 0.0034; 95% CI, 0.6-2.9) than in the Control-S (11.1 ± 0.8 g/dl). However, the H23.0%-S was not significant. CONCLUSIONS: Inhalation of 1.2% H2 gas protected the endothelial glycocalyx and prolonged survival time during hemorrhagic shock. Therapeutic efficacy might vary depending on the concentration.

Characteristics of false-positive alerts on transcranial motor evoked potential monitoring during pediatric scoliosis and adult spinal deformity surgery: an "anesthetic fade" phenomenon.

OBJECTIVE: Transcranial motor evoked potential (TcMEP) monitoring may be valuable for predicting postoperative neurological complications with a high sensitivity and specificity, but one of the most frequent problems is the high false-positive rate. The purpose of this study was to clarify the differences in the risk factors for false-positive TcMEP alerts seen when performing surgery in patients with pediatric scoliosis and adult spinal deformity and to identify a method to reduce the false-positive rate. METHODS: The authors retrospectively analyzed 393 patients (282 adult and 111 pediatric patients) who underwent TcMEP monitoring while under total intravenous anesthesia during spinal deformity surgery. They defined their cutoff (alert) point as a final TcMEP amplitude of ≤ 30% of the baseline amplitude. Patients with false-positive alerts were classified into one of two groups: a group with pediatric scoliosis and a group with adult spinal deformity. RESULTS: There were 14 cases of false-positive alerts (13%) during pediatric scoliosis surgery and 62 cases of false-positive alerts (22%) during adult spinal deformity surgery. Compared to the true-negative cases during adult spinal deformity surgery, the false-positive cases had a significantly longer duration of surgery and greater estimated blood loss (both p < 0.001). Compared to the true-negative cases during pediatric scoliosis surgery, the false-positive cases had received a significantly higher total fentanyl dose and a higher mean propofol dose (0.75 ± 0.32 mg vs 0.51 ± 0.18 mg [p = 0.014] and 5.6 ± 0.8 mg/kg/hr vs 5.0 ± 0.7 mg/kg/hr [p = 0.009], respectively). A multivariate logistic regression analysis revealed that the duration of surgery (1-hour difference: OR 1.701; 95% CI 1.364-2.120; p < 0.001) was independently associated with false-positive alerts during adult spinal deformity surgery. A multivariate logistic regression analysis revealed that the mean propofol dose (1-mg/kg/hr difference: OR 3.117; 95% CI 1.196-8.123; p = 0.020), the total fentanyl dose (0.05-mg difference; OR 1.270; 95% CI 1.078-1.497; p = 0.004), and the duration of surgery (1-hour difference: OR 2.685; 95% CI 1.131-6.377; p = 0.025) were independently associated with false-positive alerts during pediatric scoliosis surgery. CONCLUSIONS: Longer duration of surgery and greater blood loss are more likely to result in false-positive alerts during adult spinal deformity surgery. In particular, anesthetic doses were associated with false-positive TcMEP alerts during pediatric scoliosis surgery. The authors believe that false-positive alerts during pediatric scoliosis surgery, in particular, are caused by "anesthetic fade."

Assessment of cerebral and renal autoregulation using near-infrared spectroscopy under normal, hypovolaemic and postfluid resuscitation conditions in a swine model: An observational study.

BACKGROUND: The impact of blood pressure changes on tissue oxygenation differs between vital organs and with blood volume conditions. OBJECTIVE: To assess cerebral and renal autoregulation simultaneously and compare the impact of blood pressure, hypovolaemia and fluid resuscitation on tissue oxygenation using near-infrared spectroscopy. DESIGN: Animal observational study. SETTING: An animal laboratory in Hamamatsu University School of Medicine, Hamamatsu, Japan, from April 2018 to August 2018. ANIMALS: Fifteen pigs, (mean ±â€ŠSD) 25.2 ±â€Š0.4 kg. INTERVENTIONS: The pigs were anaesthetised with 2.5% isoflurane and phenylephrine 0.5, 1, 2 and 5 µg kg min was administered in a stepwise fashion at 10-min intervals (baseline), followed by similar administration of sodium nitroprusside. Hypovolaemia was induced by a 600-ml bleed (33% of estimated total blood volume). Then phenylephrine was administered again (same protocol). Hypovolaemia was reversed by infusion of 600-ml hydroxyethyl starch. Phenylephrine and sodium nitroprusside were then administered again (same protocol). MAIN OUTCOME MEASURES: Average of the relation between mean arterial pressure (MAP) and cerebral or renal tissue oxygenation index (TOI) and individual TOI response during vasoactive drug infusions. RESULTS: The average relationship between MAP and cerebral or renal TOI both showed classic autoregulation patterns, whereas the renal TOI was more pressure-dependent than the cerebral TOI. Hypovolaemia shifted the relationship downward, reducing the cerebral and renal TOIs by approximately 5 and 20%, respectively, at similar MAPs. Subsequent fluid resuscitation preserved the autoregulatory pattern in both organs, not changing cerebral TOI but reducing renal TOI to 10% under baseline. TOI responses in both organs included paradoxical changes (tissue oxygenation changed inversely with MAP) in 60% of animals. Animals with paradoxical reactions maintained more stable cerebral and renal oxygenation. CONCLUSION: Renal oxygenation is more pressure-dependent than pressure-tolerant cerebral oxygenation, and autoregulation is not robust. Renal oxygenation decreased four-fold compared with cerebral oxygenation during hypovolaemia and two-fold during isovolaemic anaemia. Thus, paradoxical responses are part of normal autoregulatory function and beneficial for maintaining stable oxygenation.

Effective Dose of Landiolol, an Ultra-Short-Acting ß-Blocker, to Decrease Heart Rate During On-Pump, Beating Coronary Artery Bypass Grafting.

OBJECTIVE: Decreasing the heart rate (HR) using landiolol, an ultra-short-acting ß-blocker, is helpful for completing a meticulous distal anastomosis during on-pump or off-pump, beating coronary artery bypass grafting (CABG) surgery. We determine the effectiveness of landiolol to decrease the HR because the most effective dose has not been established. DESIGN: Observational open-label pharmacodynamics cohort study. SETTING: Single center, Hamamatsu University Hospital. PARTICIPANTS: 28 patients undergoing on-pump, beating CABG. INTERVENTIONS: Landiolol 5 µg/kg/min was started (time 0) and then increased to 15, 25, and 35 µg/kg/min at 10-min intervals during left internal thoracic artery (LITA) to left anterior descending artery (LAD) anastomosis. MEASUREMENTS AND MAIN RESULTS: Pharmacodynamics were characterized using a sigmoidal inhibitory maximum effect model to determine the percent decrease in HR according to the landiolol dose. Baseline (mean  ±â€¯ SD) HR (85 ±â€¯10 beats/min) decreased to 81 ±â€¯9, 71 ±â€¯10, 67 ±â€¯9, and 67 ±â€¯9 beats/min, respectively, at the four landiolol infusion points evaluated. Estimated maximum percent decrease in HR from the baseline effective dose value (ED0) was -21.5 (-25.3 to -17.8) [mean (95% confidence interval)]%. ED50, ED90, and ED95 were 9.5 (9.0-10.1), 25.0 (22.5-27.6), and 35.2 (30.3-40.1) µg/kg/min, respectively. CONCLUSIONS: Landiolol maximally decreased HR just over 20% of the baseline HR. Hence, landiolol 25 µg/kg/min is likely a sufficient dose during LITA-LAD anastomosis during on-pump, beating CABG.

Intracranial Space-occupying Lesion Inducing Intracranial Hypertension Increases the Encephalographic Effects of Isoflurane in a Swine Model.

BACKGROUND: Patients with a brain tumor are susceptible to the hypnotic effect of anesthetics depending on the tumor's size. We investigated whether intracranial space-occupying lesions (ICSOLs) inducing intracranial hypertension increase isoflurane's effect on electroencephalographic (EEG) results. MATERIALS AND METHODS: After anesthetic induction with isoflurane, 11 swine were studied with regard to isoflurane's effect on EEGs at 0.5% to 2.0% inhalational concentration at sequential stages: baseline 1, ICSOL 1, baseline 2, ICSOL 2, baseline 3. At each ICSOL stage, an intracranial epidural balloon catheter was inflated and the intracranial pressure maintained at twice the baseline pressure. The balloon was deflated after each ICSOL stage (baselines 2 and 3). A 95% spectral edge frequency (SEF), which correlates with anesthetic hypnosis, was used to measure isoflurane's effect. Pharmacodynamics was characterized using a sigmoidal inhibitory maximum effect model for the SEF versus end-tidal concentration. RESULTS: ICSOL shifted the relations between SEF and the effect-site concentration (Ce) downward. Baseline and 50% of the maximum spectral edge effect levels significantly decreased during balloon inflation. The Ce that produced SEF=15 was 1.12 (1.04-1.20) (mean [95% confidence interval])% for baseline 1; 0.92 (0.81-1.03) for ICSOL 1; 1.02 (0.94-1.11) for baseline 2; 0.88 (0.82-0.94) for ICSOL 2; 1.05 (0.93-1.17) for baseline 3. Isoflurane's effect on EEGs increased during balloon inflation, with the alteration tending to recover after balloon deflation. CONCLUSIONS: ICSOLs inducing intracranial hypertension increase the EEG effect of isoflurane, and external compression from the brain surface enhances the anesthetic hypnosis despite minimum brain injury.

Dobutamine, a ß1 Adrenoceptor Agonist, Increases Cerebral Oxygenation During Acute Anemia and Apneic Hypoxia.

BACKGROUND: ß1 blockers increase the risk of cerebral hypoxia during acute anemia and apneic hypoxia. We hypothesized that ß1 stimulants conversely increase cerebral tolerance to anemia and hypoxia. METHODS: After induction with isoflurane, twelve swine (mean ± SD: 25.2 ± 0.6 kg) received 200 µg kg-1 min-1 landiolol and 20 µg kg-1 min-1 dobutamine. Reversal of the order of drug administration was performed in six animals each. Before and during each drug infusion, apnea was induced until reaching <70% oxygen saturation (SpO2) after 5 min of 100% oxygen ventilation. Hemodynamic and blood gas variables were measured, and the cerebral and peripheral tissue oxygenation index (TOI) was recorded by near-infrared spectroscopy (apnea experiment). Following this, anemia (isovolemic hemodilution) was induced and apnea experiments were conducted in three stages, similarly to those before anemia. RESULTS: Dobutamine increased cerebral TOI before apnea (fraction of inspired oxygen [FiO2]: 1.0), at 1 min after apnea, and at SpO2 < 70% by 7.9, 8.8, and 3.9%. Landiolol decreased TOI by 0.8, 2.6, and 4.4% from the respective values at baseline. During anemia, these changes decreased with dobutamine and increased with landiolol administration. Dobutamine (or landiolol) shifted the relationship between TOI and arterial hemoglobin oxygen saturation or arterial partial pressure of oxygen to the right (or left) and increased (or decreased) TOI at similar arterial blood oxygenation. CONCLUSIONS: Dobutamine increases cerebral oxygenation during hypoxia and/or anemia and might be effective in improving neurological outcomes in ischemic cerebral injury.

Use of a Short-Acting ß1 Blocker During Endotoxemia May Reduce Cerebral Tissue Oxygenation if Hemodynamics are Depressed by a Decrease in Heart Rate.

BACKGROUND: A decrease in heart rate (HR) using a short-acting ß blocker has potential benefits in sepsis; however, depression of hemodynamics and reduction of cerebral oxygenation may also occur in endotoxemia. METHODS: Seventeen swine were allocated to landiolol or control groups. In the landiolol group, the dose was sequentially changed from 0 to 40 to 200 µg kg min, and stopped. Hemodynamics, blood variables, and the cerebral tissue oxygenation index (TOI) were recorded by near infrared spectroscopy at each dose. Lipopolysaccharide (LPS) was then administered continuously at 1 µg kg h after a 100 µg bolus administration. After 30 and 150 min, as two severity stages of endotoxemia (endotoxemia 1 and 2), landiolol was administered as above and measurements were made. In the control group, landiolol was not administered, but measurements were made. RESULTS: LPS increased HR and landiolol decreased HR, with similar effects in each endotoxemia stage. In endotoxemia 1, LPS decreased stroke volume (SV), but landiolol restored SV to a value similar to that before endotoxemia, and did not decrease cardiac output (CO), even at 200 µg kg min. In contrast, landiolol did not restore SV in endotoxemia 2, resulting in a decrease in CO and mean arterial pressure, accompanied with a dose-dependent decrease in TOI. CONCLUSIONS: A short-acting ß blocker has various hemodynamic effects in endotoxemia. Use of a short-acting ß blocker during endotoxemia may reduce cerebral tissue oxygenation if hemodynamics are depressed by a decrease in HR.

Time-dependent changes in epidural catheter aspirate after injection of a local anesthetic.

STUDY OBJECTIVE: A glucose check is used for investigation of a suspected accidental dural puncture in epidural anesthesia. However, glucose-positive clear fluid is sometimes aspirated from an epidural catheter in cases without clinical evidence of puncture. The goal of the study was to investigate time-dependent changes in the aspirate composition after injection of a local anesthetic into the epidural space. DESIGN: Observational study. SETTING: Operating rooms at Hamamatsu University Hospital. PATIENTS: The subjects were 30 patients (ASA I or II) undergoing surgery with combined epidural and general anesthesia. INTERVENTIONS: After epidural injection of local anesthetics, aspiration through the catheter was performed every 10min until fluid could not be aspirated. pH, Na, K, Cl, Ca and glucose were measured in fluid samples using a blood gas analysis apparatus. MAIN RESULTS: No patients had pain or clinical signs suggesting dural puncture throughout the perioperative period. Fluid aspiration was possible in 15 patients (50%) after 10min and in 7, 3, 2 and 2 patients after 20, 30, 40 and 50min, respectively. Glucose was detected in each aspirated fluid sample and gradually increased with time to become closer to the level in cerebrospinal fluid (CSF). Each electrolyte also changed to approach the level found in CSF. CONCLUSIONS: A glucose check may increase the risk of a false-positive finding for accidental dural puncture with increasing time after local anesthetic injection. Conversely, detection of glucose at the time of epidural catheter placement may provide useful information for detection of accidental dural puncture.