Ketamine and propofol have opposite effects on postanesthetic sleep architecture in rats: relevance to the endogenous sleep-wakefulness substances orexin and melanin-concentrating hormone.

BACKGROUND: Anesthesia and surgery disturb sleep. Disturbed sleep adversely affects postoperative complications involving the cardiovascular system, diabetes, and infection. General anesthetics share neuronal mechanisms involving endogenous sleep-wakefulness-related substances, such as orexin (OX) and melanin-concentrating hormone (MCH). We evaluated changes in sleep architecture and the concentration of OX and MCH during the peri-anesthetic period. METHODS: To examine sleep architecture, male Sprague-Dawley rats weighing 350-450 g received ketamine 100 mg/kg (n = 9) or propofol 80 mg/kg (n = 6) by intraperitoneal injection. Electroencephalography was recorded from 2 days pre- to 5 days postanesthesia. To quantify levels of OX and MCH, 144 similar rats received the same doses of ketamine (n = 80) or propofol (n = 64). Brain concentrations of these substances were determined at 0, 20, 60, and 120 min after anesthetic administration. RESULTS: Ketamine decreased OX content in the hypothalamus during the anesthesia period. OX content was restored to pre-anesthesia levels in the hypothalamus and pons. Both anesthetics increased brain MCH content in the postanesthetic period, with the degree of increase being greater with propofol. Ketamine enhanced wakefulness and inhibited non-rapid eye movement sleep (NREMS) immediately after anesthesia. Conversely, propofol inhibited wakefulness and enhanced NREMS in that period. Ketamine inhibited wakefulness and enhanced NREMS during the dark phase on the first postanesthesia day. CONCLUSIONS: Anesthetics affect various endogenous sleep-wakefulness-related substances; however, the modulation pattern may depend on the type of anesthetic. The process of postanesthetic sleep disturbance was agent specific. Our results provide fundamental evidence to treat anesthetic-related sleep disturbance.

[Analgesic efficacy and clinical safety of intraperitoneal instillation combined with rectus sheath block using ropivacaine for pain relief after laparoscopic gynecological surgery].

BACKGROUND: The aim of this study was to evaluate the analgesic efficacy and safety of rectus sheath block combined with intraperitoneal instillation using two doses of ropivacaine in patients undergoing laparoscopic gynecological surgery. METHODS: Altogether 53 consenting women were randomized to receive intraperitoneal infiltration with 0.25% ropivacaine or 0.5% ropivacaine followed by rectus sheath block with 0.375% ropivacaine. The outcomes of clinical safety were measured using plasma concentration of local anesthetics and occurrence of toxic symptoms. The analgesic efficacy was assessed using numerical rating scales for pain and morphine consumption up to 24 hours after surgery. RESULTS: Patients' baseline characteristics, surgical factors, and analgesic outcomes were comparable between the two groups. Although peak plasma concentration of ropivacaine was significantly higher in patients receiving 0.5% ropivacaine, none of analyzed concentrations was above the toxic ones. Besides, no patients showed any symptoms of local anesthetic toxicity. CONCLUSIONS: The present study showed that the combination of rectus sheath block with intraperitoneal instillation of ropivacaine was safe and potent enough to relieve pain after laparoscopic surgery.

Quantitative measurement of blood remifentanil concentration: development of a new method and clinical application.

We have developed a new detection method of blood remifentanil concentration using a gas chromatography-mass spectrometry(GC-MS) with fentanyl as the internal standard(IS). The detection was performed at m/z 168 and 245 for remifentanil and fentanyl, respectively. In addition, the retention times of remifentanil and fentanyl were 5 min 45 s and 6 min 51 s, respectively. The standard curve of relationship between remifentanil concentration and the ratio of the peak area of remifentanil to fentanyl was satisfactorily fitted as linear regression (R(2) = 0.998, p < 0.01). Intra- and inter-assay CV was 10.5 and 11.5 %, respectively. In the clinical setting, 21 adult patients undergoing elective surgery under propofol-remifentanil TIVA were enrolled. To determine blood remifentanil concentrations, arterial blood was obtained at 0-30 min after cessation of remifentanil infusion at 0.2 µg/kg/min. Blood samples were given into sample tubes(chilled on ice) containing citric acid 50 % 60 µl which inactivates all esterase, and then stored at -20 °C until assay. Measured blood remifentanil concentration was 3.59 ± 0.74 ng/ml at the end of remifentanil infusion, and the ime for a decrease in blood remifentanil concentration by half was ~2 min. Remifentanil concentration was below the detection limit 30 min after the cessation. Thus, we have confirmed that this new method is clinically applicable.

Brief reports: plasma ropivacaine concentrations after ultrasound-guided rectus sheath block in patients undergoing lower abdominal surgery.

A rectus sheath block can provide postoperative analgesia for midline incisions. However, information regarding the pharmacokinetics of local anesthetics used in this block is lacking. In this study, we detail the time course of ropivacaine concentrations after this block. Thirty-nine patients undergoing elective lower abdominal surgery were assigned to 3 groups receiving rectus sheath block with 20 mL of different concentrations of ropivacaine. Peak plasma concentrations were dose dependent, and there were no significant differences in the times to peak plasma concentrations. The present data also suggested a slower absorption kinetics profile for ropivacaine after rectus sheath block than other compartment blocks.

A marked increase in gastric fluid volume during cardiopulmonary bypass.

Major physiological stress occurs during cardiac surgery with cardiopulmonary bypass. This is related to hypothermia and artificial organ perfusion. Thus, serious gastrointestinal complications, particularly upper gastrointestinal bleeding, sometimes follow cardiac surgery. We have compared the antisecretory effects of a preanesthetic H(2) antagonist (roxatidine, cardiopulmonary bypass-H(2) group, n = 15) and a proton pump inhibitor (rabeprazole, cardiopulmonary bypass-PPI group, n = 15) in patients undergoing cardiac surgery with cardiopulmonary bypass, and also compared in patients undergoing a off-pump coronary artery bypass graft surgery (off-pump cardiopulmonary bypass-H(2) group, n = 15). Gastric pH (5.14 ± 0.61) and gastric fluid volume (13.2 ± 2.4 mL) at the end of surgery in off-pump cardiopulmonary bypass-H(2) groups was significantly lower and higher than those in both cardiopulmonary bypass-H(2) (6.25 ± 0.54, 51.3 ± 8.0 mL) and cardiopulmonary bypass-PPI (7.29 ± 0.13, 63.5 ± 14.8 mL) groups, respectively although those variables did not differ between groups after the induction of anesthesia. Plasma gastrin (142 ± 7 pg/mL) at the end of surgery and maximal blood lactate levels (1.50 ± 0.61 mM) in off-pump cardiopulmonary bypass-H(2) group were also significantly lower than those in both cardiopulmonary bypass-H(2) (455 ± 96 pg/mL, 3.97 ± 0.80 mM) and cardiopulmonary bypass-PPI (525 ± 27 pg/mL, 3.15 ± 0.44 mM) groups, respectively. In addition, there was a significant correlation between gastric fluid volume and maximal blood lactate (r = 0.596). In conclusion, cardiopulmonary bypass may cause an increase in gastric fluid volume which neither H(2) antagonist nor PPI suppresses. A significant correlation between gastric fluid volume and maximal blood lactate suggests that gastric fluid volume may predict degree of gastrointestinal tract hypoperfusion.

Leg massage therapy promotes psychological relaxation and reinforces the first-line host defense in cancer patients.

PURPOSE: Patients with cancer suffer a wide range of physical symptoms coupled with psychological stress. Moreover, cancer chemotherapy induces immunosuppression and consequently causes respiratory infections. Massage therapy has been reported to reduce symptoms in cancer patients via an increase in psychosocial relaxation and to enhance and/or improve immune function. METHODS: In the present study, we determined whether leg massage could induce psychosocial relaxation and activate the first line of the host defense system. To assess effects of rest and leg massage, 15 healthy volunteers rested on a bed for 20 min on the first day, and 3 days later the subjects received a standardized massage of the legs for 20 min with nonaromatic oil. Twenty-nine cancer patients also received the same standardized massage of the legs. Anxiety/stress was assessed before and just after the rest or the massage using the State-Trait Anxiety Inventory (STAI-s) and visual analogue scale (VAS). To evaluate oral immune function, salivary chromogranin A (CgA) and secretory immunoglobulin A (sIgA) levels were measured. RESULTS: In healthy volunteers, rest significantly reduced VAS by 34% and increased sIgA by 61%. In contrast, leg massage significantly reduced both STAI-s and VAS by 24% and 63%, and increased both sIgA and CgA by 104% and 90%, respectively. In cancer patients, leg massage significantly decreased both STAI-s and VAS by 16% and 38%, and increased both salivary CgA and sIgA by 33% and 35%, respectively. CONCLUSION: Leg massage may promote psychosocial relaxation and reinforce a first-line host defense with an increase in secretion of antimicrobial peptides.

Plasma orexin A increases at emergence from sevoflurane-fentanyl anesthesia in patients undergoing ophthalmologic surgery.

Central orexinergic and noradrenergic neurons are involved in the control of sleep and wakefulness. In addition, previous reports suggest that both neurons may have an important role to play in general anesthesia. In the present study, we have determined whether general anesthesia would affect plasma orexin A (OXA) and norepinephrine concentrations. Twelve patients scheduled for elective ophthalmic surgery under general anesthesia with sevoflurane, fentanyl and vecuronium were studied. Arterial blood was collected before and 1 and 2h after induction of anesthesia and at emergence to measure plasma OXA, cortisol, norepinephrine and epinephrine concentrations. During anesthesia the inhalational concentration of sevoflurane was changed to maintain the bispectral index between 40 and 50. Plasma OXA, cortisol, norepinephrine and epinephrine did not change during anesthesia but significantly increased after emergence compared to pre-anesthesia (from 14.8+/-1.7 to 21.4+/-1.7 pM, p<0.01, from 26.5+/-5.2 to 52.8+/-6.0 pM, p<0.01, from 263+/-46 to 513+/-89 pM, p<0.01, and from 1239+/-120 to 1631+/-203 pM, p<0.01, respectively). There were significant correlations of plasma OXA with cortisol (r=0.334, p<0.05) and epinephrine (r=0.292, p<0.05) but not with norepinephrine. In conclusion we found that plasma OXA significantly increased at emergence from sevoflurane-fentanyl anesthesia and this was probably via activation of the hypothalamic-pituitary-adrenal axis.

Efficacy of a single 24-hour pre-anesthetic dose of proton pump inhibitors.

BACKGROUND AND AIM: The H(2) receptor antagonist roxatidine is routinely used as an oral pre-anesthetic medication in surgical patients at night and 2 h before surgery. In the present study, we have compared the effects of roxatidine, rabeprazole and lansoprazole given singly at night as an alternative to the standard double roxatidine medication. METHODS: 120 adult patients undergoing urological surgery were randomly assigned to three groups: roxatidine, rabeprazole and lansoprazole (n = 40 each). Following induction of anesthesia, gastric fluid was obtained by aspiration using a syringe to measure pH and volume of gastric contents. RESULTS: Gastric volume (14.1 +/- 1.9 mL) in the lansoprazole group was significantly larger than that in roxatidine (8.6 +/- 1.7 mL) and rabeprazole (7.5 +/- 1.1 mL) groups (P < 0.05). Gastric pH in lansoprazole group (4.10 +/- 0.38) was also significantly lower than that in the roxatidine group (5.41 +/- 0.31, P < 0.05). The numbers of patients with critical factors for acid aspiration pneumonia (gastric pH < 2.5 or volume > 25 mL) in the lansoprazole group was significantly higher than in the roxatidine group (P < 0.05). Gastric pH and volume in all groups were constant even in the afternoon. CONCLUSION: Single rabeprazole (but not lansoperazole) medication may be a suitable alternative to standard roxatidine for prophylaxis of acid aspiration pneumonia.

The efficacy of preanesthetic proton pump inhibitor treatment for patients on long-term H2 antagonist therapy.

UNLABELLED: We previously reported that H2-antagonist medication given for longer than 4 wk may produce complete tolerance to preanesthetic H2 antagonist therapy. In this study, we evaluated the efficacy of preanesthetic proton pump inhibitor (PPI; oral rabeprazol) use in patients receiving regular H2-antagonist (oral famotidine) therapy for more than 4 wk. Forty-eight patients with assumed complete tolerance to H2 antagonists undergoing elective surgery were recruited and randomly assigned to receive either a preanesthetic PPI (rabeprazol 20 mg; n = 24) or H2-antagonist (H2 group; roxatidine 75 mg; n = 24) at 9:00 pm on the day before surgery and 2 h before the induction of anesthesia. Volume of gastric contents and pH values were measured after the induction of anesthesia. Gastric pH value in the PPI group (5.38 +/- 2.42) was significantly higher than in the H2 group (3.27 +/- 1.98; P < 0.01). Gastric volume in the PPI group (8.6 +/- 1.5 mL) was significantly smaller than in the H2 group (15.4 +/- 2.8 mL; P < 0.05; cf. PPI). Fourteen patients in the H2 group were at risk of acid aspiration pneumonia (gastric pH <2.5 or volume >25 mL), whereas only four patients in the PPI group (P < 0.05) were at risk. These data suggest that in patients receiving H2-antagonist therapy for longer than 4 wk, prophylaxis for acid aspiration pneumonia should include preanesthetic PPI medication. IMPLICATIONS: We previously reported that more than 4 wk of administration of H2-antagonists may produce a full tolerance to preanesthetic H2-antagonists. The present study suggests that a proton pump inhibitor may be effective for prophylaxis of acid aspiration pneumonia in patients showing the full tolerance to H2 antagonists.

Regular use of H2 blockers reduces the efficacy of roxatidine to control gastric pH and volume.

PURPOSE: H(2) antagonist premedication is common in surgical patients to control gastric pH and volume. However, several reports suggest that long-term medication may produce tolerance. Therefore, we studied the efficacy of a preanesthetic H(2) antagonist (oral roxatidine) in patients on regular H(2) antagonist therapy. METHODS: Forty-eight patients undergoing elective surgery were studied and grouped according to medication: those on no medication (control group) and those receiving H(2)-antagonists for less than two weeks (< or =2 w group), between two and four weeks (2-4 w group) and for longer than four weeks (> or =4 w group; n =12 each). All patients were given oral roxatidine as anesthetic premedication. Gastric volume and pH were measured after induction of anesthesia. Arterial blood was simultaneously collected for measurement of plasma gastrin levels using an enzyme-linked immunosorbent assay RESULTS: We observed a significant decrease and increase in, respectively, gastric pH and volume (mL) in the < or =2 w group [6.50 +/- 0.43 (NS) and 11.6 +/- 10.3 (NS)], 2-4 w group [4.77 +/- 2.11 (P < 0.01) and 14.1 +/- 10.8 (P < 0.05)], > or =4 w group [2.32 +/- 1.46 (P < 0.01) and 22.2 +/- 14.2 (P < 0.01)] compared to patients in the control group (6.35 +/- 1.32 and 4.9 +/- 4.7). Plasma gastrin levels were decreased with increasing time on medication with a significant difference (46%) observed after two weeks' treatment. In addition, there was a significant correlation between gastric pH and plasma gastrin levels (r = 0.43, P < 0.01). CONCLUSION: These data suggest that regular H(2) antagonist treatment for longer than two weeks may produce tolerance to pre-anesthetic H(2) antagonist administration.

The interaction between fentanyl and propofol during emergence from anesthesia: monitoring with the EEG-Bispectral index.

STUDY OBJECTIVE: To investigate the effect of different plasma levels of fentanyl on the concentration of propofol and the Bispectral Index (BIS) required for patients to regain consciousness and orientation following surgery. DESIGN: Prospective, open-label study. SETTING: Operating room of a university hospital. PATIENTS: 28 patients, aging 20 to 50 years, scheduled for elective, 1- to 4-hour surgeries under general anesthesia. INTERVENTIONS: BIS was continuously monitored from bifrontal montage (At1-Fpz and At2-Fpz) using an Aspect A-1,050 EEG system (Aspect, Natick, MA). Anesthesia was induced with bolus injections of fentanyl 2 microg/kg and propofol 2 mg/kg, and maintained with intermittent injections of fentanyl and constant infusion of propofol. Propofol infusion was stopped at the end of surgery. MEASUREMENTS: Consciousness and orientation were assessed as clinical endpoints once every 2 minutes following the end of the surgery. Blood samples were extracted for plasma propofol and fentanyl concentrations (PCp and FCp, respectively), and BIS values were recorded when patients regained consciousness and orientation. Patients were allocated to one of three groups depending on FCp on awakening: Group 1, FCp > 1 microg/L (n = 8); Group 2, FCp < 1 microg/L and >0.45 microg/L (n = 9); and Group 3, FCp < 0.45 microg/L (n = 11). PCp, BIS, recovery time, and other data were compared between the three groups. MAIN RESULTS: Demographic values, duration of surgery, and consumption of propofol and fentanyl were not different between the three groups. Group 3 patients regained consciousness with significantly higher propofol concentration (mean PCp = 3.2 mg/L) compared with those in Groups 1 and 2 (p < 0.05). However, the BIS values at both recovery endpoints were not different among the three groups. CONCLUSIONS: The plasma levels of fentanyl affect the concentrations of propofol required for patients to regain consciousness. The BIS values for wakefulness are unaltered at the different combinations of propofol and fentanyl concentrations. Thus, the BIS appears to be a useful and consistent indicator for level of consciousness during emergence from propofol/fentanyl intravenous anesthesia.