Isoflurane-nitrous Oxide Anesthesia Research Articles

Correction to: Cerebrovascular CO2 reactivity during isoflurane-nitrous oxide anesthesia in patients with chronic renal failure.

In the original publication of the article, the first sentence was published incorrectly under the section "Patients and preoperative assessment". The correct sentence should read as, "The Yamaguchi University Graduate School of Medicine Ethics Committee for Human Study approved the study protocol (18th August 2004: H16-71)".

Cerebrovascular CO2 reactivity during isoflurane-nitrous oxide anesthesia in patients with chronic renal failure.

We assessed the cerebrovascular CO2 reactivity (CO2R) in chronic renal failure (CRF) patients without diabetes mellitus (DM), uncontrolled hypertension, peripheral vascular disease, or neurological disease under isoflurane-nitrous oxide anesthesia. Forty-nine patients undergoing surgery, including 36 CRF patients (30 receiving dialysis and six pre-dialysis patients) and 13 patients without CRF (controls). Middle cerebral artery flow velocity (VMCA) was measured by transcranial Doppler ultrasonography at an end-tidal CO2 of 35 to 45mmHg. CO2R was calculated as an absolute value (change in VMCA per mmHg PaCO2) and a relative value (absolute CO2R/baseline VMCA×100). Factors associated with CO2R were evaluated simultaneously. Despite no significant differences in the absolute and relative values of CO2R between the CRF (mean 2.5cm/s/mmHg; median 5.0%/mmHg) and control (2.4cm/s/mmHg; 5.0%/mmHg) groups, blood urea nitrogen (BUN) concentrations in the CRF group correlated inversely with both absolute and relative CO2R. BUN concentration was higher (mean 72 versus 53mg/dl, p=0.006) and relative CO2R was lower (mean 2.6 versus 5.7%/mmHg, p=0.011) in patients with pre-dialysis CRF (n=6) versus CRF patients receiving dialysis (n=30). CO2R in CRF patients was not significantly different from that in controls. However, in CRF patients with high BUN concentrations, CO2R might be impaired, leading to reduced cerebrovascular reserve capacity. Because DM is a major cause of CRF and we excluded DM patients, our results might not be applicable to patients with DM-induced CRF.

Pregnancy-induced changes in the circadian expression of hepatic clock genes: implications for maternal glucose homeostasis.

Adaptations in maternal carbohydrate metabolism are particularly important in pregnancy because glucose is the principal energy substrate used by the fetus. As metabolic homeostasis is intricately linked to the circadian system via the rhythmic expression of clock genes, it is likely that metabolic adaptations during pregnancy also involve shifts in maternal circadian function. We hypothesized that maternal adaptation in pregnancy involves changes in the hepatic expression of clock genes, which drive downstream shifts in circadian expression of glucoregulatory genes. Maternal liver and plasma (n = 6-8/group) were collected across 24-h periods (0800, 1200, 1600, 2000, 0000, 0400) from C57Bl/6J mice under isoflurane-nitrous oxide anesthesia prior to and on days 6, 10, 14 and 18 of pregnancy (term = day 19). Hepatic expression of clock genes and glucoregulatory genes was determined by RT-qPCR. Hepatic clock gene expression was substantially altered across pregnancy, most notably in late gestation when the circadian rhythmicity of several clock genes was attenuated (≤64% reduced amplitude on day 18). These changes were associated with a similar decline in rhythmicity of the key glucoregulatory genes Pck1, G6Pase, and Gk, and by day 18, Pck1 was no longer rhythmic. Overall, our data show marked adaptations in the liver clock during mouse pregnancy, changes that may contribute to the altered circadian variation in glucoregulatory genes near term. We propose that the observed reduction of daily oscillations in glucose metabolism ensure a sustained supply of glucose to meet the high demands of fetal growth.

Postoperative Nausea and Vomiting in Day Care Patients: A Comparative Randomized Controlled Trial of Total Intravenous Anesthesia with Propofol, Air, and Oxygen vs Inhalation Anesthesia with Isoflurane and Nitrous Oxide

ABSTRACTIntroductionWe compared the incidence of postoperative nausea and vomiting (PONV) after total intravenous anesthesia (TIVA) using propofol–air to inhalational anesthesia with isoflurane–nitrous oxide in day care patients at a tertiary care academic institution.Materials and methodsWe randomized 60 patients and assigned to either group I (inhalational anesthesia with isoflurane– nitrous oxide) or group II (TIVA with propofol–air). Incidence of PONV, use of anti-emetics, and duration of stay in the recovery were recorded for 72 hours by blinded observers.ResultsTotal intravenous anesthesia reduced the PONV up to 72 hours by 27% among our patients (from 37 to 10%, p < 0.001). This effect was seen more in the early postoperative period. Overall, 13.3% of patients in the group I received antiemetic compared to 40% in group II. In our study, patients without PONV were discharged from the recovery room 15 minutes earlier after TIVA than after isoflurane and N2O anesthesia.ConclusionTotal intravenous anesthesia with propofol and air resulted in a reduction of PONV compared with iso-flurane–nitrous oxide anesthesia. Overall, patients in group I required less rescue antiemetic, compared to group II. Total intravenous anesthesia resulted in shorter stay in the postoperative anesthetic care unit compared to isoflurane–N2O group.How to cite this articleSandhya A, Mamatha R, Banerjee A, Sahajananda H. Postoperative Nausea and Vomiting in Day Care Patients: A Comparative Randomized Controlled Trial of Total Intravenous Anesthesia with Propofol, Air, and OxygenvsInhalation Anesthesia with Isoflurane and Nitrous Oxide. J Med Sci 2015;1(4):63-68.

Cysteine Reversal of the Novel Neuromuscular Blocking Drug CW002 in Dogs

CW002 is a neuromuscular blocking drug that is inactivated by endogenous L-cysteine. This study determined the exogenous L-cysteine dose-response relationship for CW002 reversal along with acute cardiovascular effects and organ toxicity in dogs. Six dogs were each studied four times during isoflurane-nitrous oxide anesthesia and recording of muscle twitch, arterial pressure, and heart rate. CW002 (0.08 mg/kg or 9 x ED95) was injected, and the time to spontaneous muscle recovery was determined. CW002 was then administered again followed 1 min later by 10, 20, 50, or 100 mg/kg L-cysteine (1 dose/experiment). After twitch recovery, CW002 was given a third time to determine whether residual L-cysteine influenced duration. Preliminary toxicology was performed in an additional group of dogs that received CW002 followed by vehicle (n = 8) or 200 mg/kg L-cysteine (n = 8). Animals were awakened and observed for 2 or 14 days before sacrificing and anatomic, biochemical, and histopathologic analyses. L-cysteine at all doses accelerated recovery from CW002, with both 50 and 100 mg/kg decreasing median duration from more than 70 min to less than 5 min. After reversal, duration of a subsequent CW002 dose was also decreased in a dose-dependent manner. Over the studied dose range, L-cysteine had less than 10% effect on blood pressure and heart rate. Animals receiving a single 200-mg/kg dose of L-cysteine showed no clinical, anatomic, biochemical, or histologic evidence of organ toxicity. The optimal L-cysteine dose for rapidly reversing the neuromuscular blockade produced by a large dose of CW002 in dogs is approximately 50 mg/kg, which has no concomitant hemodynamic effect. A dose of 200 mg/kg had no evident organ toxicity.

Comparison of Isoflurane-nitrous Oxide Anesthesia and Isoflurane-remifentanil Anesthesia during Tympanoplasty

Nitrous oxide (N2O) may increase middle ear pressure during anesthesia, resulting in the displacement of tympanic membrane graft for tympanoplasty.This study was performed to assess the feasibility of remifentanil instead of N2O by comparing hemodynamics, recovery profiles, postoperative analgesia and complications during isoflurane-based anesthesia for tympanoplasty. Methods:Forty patientsundergoing tympanoplasty were randomly allocated to N2O-isoflurane anesthesia (group N) and remifentanil-isoflurane anesthesia (group R).In group N, N2O was used from induction to 15−30 minutes prior to grafting tympanic membrane and then N2O was changed to air.In group R, remifentanil was infused to the end of surgery.Isoflurane was used in both groups.We compared mean arterial pressure (MAP), heart rate (HR) and recovery times between groups during perioperative period.Postoperative pain, analgesic demand and nausea/vomiting during postoperative period were also compared. Results:MAP and HR were significantly higher in group N than group R at 1 minute, 5 minutes after intubation, skin incision and closure.Hypertensive and tachycardiac events were also more frequent in group N during operation.Time to spontaneous respiration was significantly shorter in group N, but times to eye opening, extubation and recovery of orientation were significantly shorter in group R.There were no significant differences in pain scores, analgesic demand and nausea/vomiting during postoperative period. Conclusions:Remifentanil can provide more stable hemodynamic status and faster emergence than N2O without significant increase of pain level, analgesic demand and adverse effects in isoflurane-based anesthesia for tympanoplasty.

Stress hormone changes in general anesthesia of long duration: isoflurane–nitrous oxide vs sevoflurane–nitrous oxide anesthesia

Study Objective There are few comparative studies of stress hormone changes during general anesthesia with long duration between isoflurane–nitrous oxide and sevoflurane–nitrous oxide anesthesia. We investigated perioperative changes of stress hormone in these two anesthetic methods with duration of more than 10 hours. Design Prospective study. Setting Operating room and high care unit of a university hospital. Patients Twenty patients with ASA physical status I or II for surgery for laryngeal or pharyngeal cancer with expected duration of more than 10 hours. Interventions Anesthesia was induced with midazolam, thiopental, and vecuronium and was maintained with sevoflurane (sevoflurane group) or isoflurane (isoflurane group) with nitrous oxide 4 L/min in oxygen 2 L/min. Measurements and Main Results Plasma concentrations of epinephrine, norepinephrine, cortisol, adrenocorticotropic hormone, and anti-diuretic hormone (ADH); serum concentrations of glucagon and insulin; and blood glucose concentration were measured before inhalation of anesthetics, after 5 and 10 hours, and at 1, 6, and 12 hours after the end of inhalation. Epinephrine and norepinephrine concentrations increased continuously during and after surgery in the isoflurane group whereas it increased only after surgery in the sevoflurane group. Both concentrations were higher in the isoflurane group during anesthesia. Cortisol increased continuously whereas adrenocorticotropic hormone increased only during surgery. Anti-diuretic hormone increased with its peak during surgery and the isoflurane group had significantly higher values than the sevoflurane group. Glucose increased both during and after surgery, insulin increased only after surgery, and glucagon decreased during surgery in both groups. Conclusions In inhalation anesthesia with the duration of more than 10 hours, isoflurane–nitrous oxide and sevoflurane–nitrous oxide had the same effects on stress hormone changes except for epinephrine, norepinephrine, and ADH. Epinephrine, norepinephrine, and ADH concentrations were higher in isoflurane–nitrous oxide anesthesia.

Impaired Acquisition of Spatial Memory 2 Weeks After Isoflurane and Isoflurane-Nitrous Oxide Anesthesia in Aged Rats

Aged rats are impaired on a spatial memory task for at least 24-48 h after isoflurane-nitrous oxide anesthesia. In this study, we tested how long the impairment lasts and investigated the role of nitrous oxide. Eighteen-month-old rats were randomized to anesthesia for 2 h with 1.2% isoflurane with or without 70% nitrous oxide or a control group (30% oxygen). Two weeks later, rats were tested daily for 14 days on a 12-arm radial maze. The number of correct choices to first error, total errors, and time to complete the maze were recorded. Rats anesthetized with 1.2% isoflurane with 70% nitrous oxide made fewer correct choices before first error (P < or = 0.05). Trends toward similar results were noted for error rate and time to complete the maze, but these did not achieve statistical significance. Post hoc analysis comparing all anesthetized rats to controls demonstrated that anesthetized rats made fewer correct choices to first error (P < or = 0.05) and took longer to complete the maze (P <or = 0.05). There were no differences in total number of errors (P < or = 0.06). Thus, spatial memory is impaired for 2 wk after general anesthesia in aged rats independent of whether nitrous oxide is used.

Hemorrhage during Isoflurane–Nitrous Oxide Anesthesia

The objective of this study was to determine whether endothelin-A receptor blockade (ETAB) impairs hemodynamic and hormonal regulation compared with controls and angiotensin II receptor blockade (AT1B) during hypotensive hemorrhage in dogs under isoflurane-nitrous oxide anesthesia. Six dogs were studied in four protocols: (1) control experiments (controls); (2) ETA blockade using ABT-627 (ETAB); (3) AT1 blockade using losartan (AT1B); and (4) combined AT1B and ETAB (AT1B + ETAB). After a 30-min awake period, isoflurane-nitrous oxide anesthesia was established (1.3 minimum anesthetic concentration). After 60 min of anesthesia, 20 ml blood/kg body weight was withdrawn within 5 min, and the dogs were observed for another hour. Thereafter, the blood was retransfused, and the dogs were observed for a final hour. Anesthesia: Cardiac output decreased in all protocols, whereas mean arterial pressure decreased more in AT1B and AT1B + ETAB than in controls and ETAB. Hemorrhage: After 60 min, cardiac output had decreased less in controls than in all other protocols. Mean arterial pressure decreased more during ETAB than in controls, but most severely during AT1B and AT1B + ETAB. Angiotensin II increased further only in controls and ETAB, whereas vasopressin and catecholamines increased similarly in all protocols. Retransfusion: Mean arterial pressure remained below controls in all protocols but was lowest when the AT1 receptor was blocked. Cardiac output fully recovered in all but the ETAB protocol. ETAB impairs long-term hemodynamic regulation after hemorrhage and retransfusion during anesthesia despite an activation of vasoconstrictive hormones. This suggests that endothelins have a role in long-term cardiovascular regulation. AT1B impairs both short- and long-term blood pressure regulation during anesthesia and after hemorrhage.

Long-term impairment of acquisition of a spatial memory task following isoflurane-nitrous oxide anesthesia in rats.

The authors demonstrated previously that isoflurane-nitrous oxide anesthesia attenuates performance improvement on an already-learned spatial memory task and that the effect persists for weeks. This experiment was designed to test the hypothesis that learning of new information is particularly susceptible to prolonged disruption after general anesthesia. Six- (n = 5) and 20- (n = 5) month-old male Fischer 344 rats were anesthetized for 2 h with 1.2% isoflurane, 70% nitrous oxide, and 30% oxygen. Age-matched control rats received 30% oxygen and 70% nitrogen (n = 5 per group). Rats breathed spontaneously, and anesthetic and oxygen concentrations were measured. Spatial learning was assessed daily for 21 days on a 12-arm radial maze (RAM) beginning 48 h after anesthesia. In a post hoc experiment to examine locomotion, swim speed was assessed in a separate group of identically treated rats (n = 3 per group) for 4 days beginning 48 h after anesthesia. Aged rats were slower to complete the maze, made fewer correct choices before first error, and made more errors at baseline than young rats (P < 0.05). Anesthesia worsened maze performance in both age groups, as evidenced by increased time to complete the maze and a decreased number of correct choices before first error (P < 0.05), but there were no statistically significant differences in total number of errors. Interestingly, there were no age-by-anesthesia interactions. Aged rats swam slower than adult rats (P < 0.001), but there were no differences between the control and anesthesia groups. Isoflurane-nitrous oxide anesthesia is associated with a persistent deficit in RAM performance that is not explained by impaired locomotion. This impairment occurs in adult and aged rats, indicating that it is not an age-specific phenomenon. Thus, RAM performance is altered after general anesthesia for longer than predicted by the pharmacology of the drugs used, which, by inference, suggests a long-term deficit in learning/memory.

Sustained Impairment of Novel Learning Following Isoflurane-Nitrous Oxide Anesthesia in Young and Aged Rats

Sustained Impairment of Novel Learning Following Isoflurane-Nitrous Oxide Anesthesia in Young and Aged Rats

Effect of renal failure and cirrhosis on the pharmacokinetics and neuromuscular effects of rapacuronium administered by bolus followed by infusion.

Recent trials indicate that rapacuronium's pharmacokinetic characteristics are influenced by both renal failure and cirrhosis but the time course of a single bolus dose of 1.5 mg/kg is affected minimally. The authors reassessed these pharmacokinetic findings and examined the time course of the same bolus dose followed by a 30-min infusion. During nitrous oxide-isoflurane anesthesia, patients with normal renal and hepatic function (n = 25), those with renal failure (n = 28), and those with cirrhosis (n = 6) received a bolus dose of rapacuronium (1.5 mg/kg) followed by a 30-min infusion adjusted to maintain 90-95% twitch depression. At 25% recovery, neostigmine was administered. Blood was sampled until 8 h after the infusion to determine concentrations of rapacuronium and its active metabolite ORG9488. Rapacuronium's pharmacokinetic parameters were determined using mixed-effects modeling. Onset and facilitated recovery of twitch depression were similar in the three groups. Patients with renal failure required 22% less rapacuronium to maintain target twitch depression during the infusion. Rapacuronium's plasma clearance was 24% smaller in renal failure and decreased 0.5%/yr of age; rapid distribution clearance was 51% smaller in men than in women. After the infusion, ORG9488 concentrations decreased markedly more slowly in patients with renal failure. Cirrhosis did not alter the pharmacokinetics of rapacuronium. Rapacuronium's plasma clearance and infusion requirement were decreased by renal failure. By dosing to maintain target twitch depression, recovery was not prolonged. Cirrhosis does not affect the pharmacokinetics or neuromuscular effects of rapacuronium. Persistence of ORG9488 in patients with renal failure might prolong recovery after rapacuronium if target twitch depression is not maintained or with administration of rapacuronium for more than 30 min.

Effects of isoflurane-nitrous oxide anaesthesia on insulin secretion in female patients

In vitro studies suggest that volatile anaesthetic agents may directly inhibit insulin secretion. It is unclear if supplementation of anaesthesia with isoflurane impairs insulin secretion. We performed a 5-g i.v. glucose tolerance test in 21 patients before and during anaesthesia which was maintained with either 1 or 2 MAC of isoflurane in nitrous oxide, or no volatile agent. The study was carried out before surgery to avoid the influence of hormonal responses to trauma. A significant glycaemic response occurred during both i.v. glucose tolerance tests in all three groups of patients. Serum insulin concentrations were measured and the acute increase in insulin concentration at 3 min and area under the curve for 15 min were calculated. Both variables decreased significantly in all three groups during the tests performed under anaesthesia compared with tests carried out before anaesthesia.

Comparative Effects of Thiopentone and Propofol on Respiratory Resistance After Tracheal Intubation

To compare the effects of propofol and thiopentone on tracheal intubation-induced bronchoconstriction, 37 patients were allocated randomly to anaesthesia with either thiopentone 4 mg kg-1 followed by a 15-mg kg-1 h-1 continuous infusion or propofol 3 mg kg-1 followed by a 9-mg kg-1 h-1 continuous infusion. Intubation was facilitated by vecuronium 0.1-0.2 mg kg-1. Respiratory system resistance (Rrs) was measured by a CP-100 pulmonary function monitor, 5 min after intubation. The 5-min post-intubation Rrs values were significantly lower in the propofol group (8.5 (SD 1.5) cm H2O litre-1 S-1) than in the thiopentone group (10.9 (3.2) cm H2O litre-1 S-1). Thirty minutes after commencing isoflurane-nitrous oxide anaesthesia, Rrs declined by 17.5 (SEM 3.6)% from baseline in the thiopentone group, but by only 1.6 (2.6)% in the propofol group. We conclude that the dose of propofol administered provided more protection against tracheal intubation-induced bronchoconstriction than an induction dose of thiopentone.

Dose-response and concentration-response relation of rocuronium infusion during propofol-nitrous oxide and isoflurane-nitrous oxide anaesthesia

Dose-response and concentration-response relation of rocuronium infusion during propofol-nitrous oxide and isoflurane-nitrous oxide anaesthesia

Surgical Pain Is Followed Not Only by Spinal Sensitization but Also by Supraspinal Antinociception

Nociception can produce segmental spinal sensitization or descending supraspinal antinociception. We assessed both types of sensory change after surgery during isoflurane-nitrous oxide anaesthesia with or without fentanyl before nociception. Patients undergoing back surgery received fentanyl 3 micrograms kg-1 (n = 15) or placebo (n = 15) before anaesthesia in a prospective, randomized, blinded study. Sensation, pain detection and tolerance thresholds to electrical stimulation were measured before operation at the arm, incision and herniated disc dermatomes (HDD) and 1, 2, 4, 6, 24 h and 5 days after operation, together with pain scores and patient-controlled morphine consumption (duration 24 h). For segmental effects, thresholds were normalized to the thresholds at a distant dermatome (arm). Raw pain thresholds were increased after operation (fentanyl > placebo) and were maximal at 4 h (pain tolerance in HDD: fentanyl +5.2 mA (+62.7%), placebo, +3.8 mA (+44.2%); P

Intraoperative EEG Changes in Relation to the Surgical Procedure During Isoflurane-Nitrous Oxide Anesthesia

Department of Anesthesiology, University Hospital Eppendorf, Hamburg, Germany; Department of Anesthesiology, Technical University Munich, Germany

Surgical Stimulation Increases Median Nerve Somatosensory Evoked Responses During Isoflurane-Nitrous Oxide Anaesthesia

Median nerve somatosensory evoked responses (MnSSER) were recorded in 15 healthy adult patients, ASA I-II, before and during orthopaedic surgery. After induction of anaesthesia with fentanyl 0.1-0.15 mg, etomidate 0.3 mg kg-1 and vecuronium 0.1 mg kg-1, anaesthesia was maintained with 0.6% isoflurane (end-tidal) and 66% nitrous oxide in oxygen. MnSSER were recorded after establishment of steady-state anaesthesia at baseline, during preparation (n = 11) and continuously after the start of surgery. For the last measurement period, four patients were excluded from analysis because additional fentanyl was required. MnSSER were recorded at Erb's point, at C6 (neck) and at the respective contralateral primary somatosensory projection area (C3' or C4'). All MnSSER waveform components remained recordable and easily identifiable during anaesthesia. During intense surgical stimulation (e.g. periosteal stimulation) the peak-to-peak amplitude N20P25 increased significantly by more than 45% (P < 0.05), whereas latencies of all components did not change over time. These data indicate that MnSSER may be reliably monitored in the intraoperative period during steady-state isoflurane-nitrous oxide anaesthesia. In addition, concurrent changes in haemodynamic variables during nociceptive stimulation support the hypothesis that reversal of isoflurane-nitrous oxide-induced suppression of MnSSER may indicate increased nociceptive input when depth of anaesthesia is inadequate.

Comparative effects of thiopentone and propofol on respiratory resistance after tracheal intubation

To compare the effects of propofol and thiopentone on tracheal intubation-induced bronchoconstriction, 37 patients were allocated randomly to anaesthesia with either thiopentone 4 mg kg-1 followed by a 15-mg kg-1 h-1 continuous infusion or propofol 3 mg kg-1 followed by a 9-mg kg-1 h-1 continuous infusion. Intubation was facilitated by vecuronium 0.1-0.2 mg kg-1. Respiratory system resistance (Rrs) was measured by a CP-100 pulmonary function monitor, 5 min after intubation. The 5-min post-intubation Rrs values were significantly lower in the propofol group (8.5 (SD 1.5) cm H2O litre-1 S-1) than in the thiopentone group (10.9 (3.2) cm H2O litre-1 S-1). Thirty minutes after commencing isoflurane-nitrous oxide anaesthesia, Rrs declined by 17.5 (SEM 3.6)% from baseline in the thiopentone group, but by only 1.6 (2.6)% in the propofol group. We conclude that the dose of propofol administered provided more protection against tracheal intubation-induced bronchoconstriction than an induction dose of thiopentone.

Mivacurium infusion during nitrous oxide-isoflurane anesthesia: A comparison with nitrous oxide-opioid anesthesia

Mivacurium infusion during nitrous oxide-isoflurane anesthesia: A comparison with nitrous oxide-opioid anesthesia