Mitsugu Fujimori

Intravenous Lidocaine as a Suppressant of Coughing during Tracheal Intubation

Effects of intravenously administered lidocaine on cough suppression during tracheal intubation under general anesthesia were evaluated in two studies. In study 1, 100 patients received either a placebo or 0.5, 1.0, 1.5, or2.0mg/kg lidocaine intravenously 1 min before tracheal intubation. All visible coughs were classified as coughing. The incidence of coughing decreased as the dose of lidocaine increased. A dose of 1 mg/kg or more of intravenous lidocaine suppressed the cough reflex significantly (P < 0.01). Coughing was suppressed completely by 2 mg/kg of intravenous lidocaine. In study 2, 108 patients received 2 mg/kg lidocaine intravenously or a placebo 1, 3, 5, 7, 10, or 15 min before intubation. The same criteria for determining whether a patient did or did not cough during tracheal intubation were used as in study 2. The incidence of coughing decreased significantly (P < 0.01) when 2 mg/kg of lidocaine was injected intravenously between 1 and 5 min before our attempting intubation. Cough reflex was suppressed completely by plasma concentrations of lidocaine in excess of 3 μg/ml.

Metabolism of a new local anesthetic, ropivacaine, by human hepatic cytochrome P450

Background Ropivacaine is a local anesthetic with a long duration of action. Although it is less toxic than bupivacaine, local anesthetic toxicity is possible when the plasma concentration is increased. Because ropivacaine is an amide‐type local anesthetic, it is metabolized by cytochrome P450 (P450) in the liver, and its elimination and plasma concentration can be dependent on the level of P450. The purpose of this investigation was to elucidate the metabolism of ropivacaine by human hepatic P450. Methods The metabolism of ropivacaine was compared using recombinant human and purified rat hepatic P450 isozymes. An inhibition study using antibodies against rat P450 was performed using hepatic microsomes from human and rat to identify which P450s are involved in ropivacaine metabolism. Results Ropivacaine was metabolized to 2′,6′‐pipecoloxylidide (PPX), 3′‐hydroxyropivacaine (3′‐OH Rop), and 4′‐hydroxyropivacaine (4′‐OH Rop) by hepatic microsomes from human and rat. PPX was a major metabolite of both human and rat hepatic microsomes. In a reconstituted system with rat P450, PPX was produced by CYP2C11 and 3A2, 4′‐OH Rop by CYP1A2, and 3′‐OH Rop by CYP1A2 and 2D1. Formation of PPX in rat hepatic microsomes was inhibited by anti CYP3A2, but not by CYP2C11 antibody, and formation of 3′‐OH Rop was inhibited by CYP1A2 and 2D1 antibodies. Anti CYP3A2 and 1A2 antibodies inhibited the formation of PPX and 3′‐OH Rop in human hepatic microsomes, respectively. Recombinant human P450s expressed in lymphoblast cells were used for further study. CYP3A4 and 1A2 formed the most PPX and 3′‐OH Rop, respectively. Ropivacaine N‐dealkylation and 3′‐hydroxylation activities correlated well with the level of CYP3A4 and 1A2 in human hepatic microsomes, respectively. Conclusions Ropivacaine was metabolized to PPX, 3′‐OH Rop, and 4′‐OH Rop by hepatic P450. PPX was a major metabolite in human hepatic microsomes. CYP3A4 was involved in producing PPX. CYP1A2 was involved in the formation of 3′‐OH Rop in human hepatic microsomes.

Intravenous lidocaine as a suppressant of coughing during tracheal intubation in elderly patients

&NA; The effects of intravenously administered lidocaine on cough suppression in elderly patients over the age of 60 yr during tracheal intubation under general anesthesia were evaluated in two studies. In the first study, 100 patients received a placebo of either 0.5, 1.0, 1.5, or 2.0 mg/kg lidocaine intravenously 1 min before tracheal intubation. All visible coughs were classified as coughing. The incidence of coughing decreased as the dose of lidocaine increased. A dose of 1.5 mg/kg or more of intravenous lidocaine suppressed the cough reflex significantly (P < 0.01). In the second study, 108 patients received 2 mg/kg lidocaine intravenously or a placebo 1, 3, 5, 7, 10, or 15 min before intubation. The same criteria for determining whether a patient did or did not cough during tracheal intubation were used as in Study 1. The incidence of coughing decreased significantly (P < 0.01) when 2 mg/kg lidocaine was injected intravenously between 1 min and 3 min before attempting intubation. The cough reflex was almost entirely suppressed by plasma concentrations of lidocaine in excess of 4 μg/mL. The results suggest that intravenous administration of lidocaine is effective in suppressing the cough reflex during tracheal intubation in elderly patients under general anesthesia, but that relatively high plasma concentrations of lidocaine may be required for suppression of coughing. (Anesth Analg 1993;77:309‐12)

Utility of colorimetric end-tidal carbon dioxide detector for monitoring during prehospital cardiopulmonary resuscitation

The purpose of this study was to evaluate a colorimetric end-tidal CO2 (ETCO2) detector (EASY CAP) as a monitor during prehospital cardiopulmonary resuscitation (CPR) without tracheal intubation. This detector was used for 121 patients during CPR with a laryngeal mask airway or face mask by authorized emergency lifesaving technicians. At 7 to 15 minutes after the initiation of CPR, ETCO was <0.5% in 30 cases (group A), 0.5% to 2.0% in 46 cases (group B) and >2.0% in 45 cases (group C). The rate of return of spontaneous circulation was 17% in group A, 24% in group B, and 48% in group C (groups A v C, P < .01). There was a significant difference in the rate of hospital admission between groups A and C. The ETCO2 value may be useful for monitoring during prehospital CPR with a laryngeal mask airway or face mask.

Administration of epidural bupivacaine combined with epidural morphine after esophageal surgery.

BACKGROUND Early tracheal extubation after esophagectomy has been postulated to reduce both morbidity rate and the cost of esophageal surgery. The purpose of this study was to determine the effect of epidural bupivacaine combined with morphine on extubation time, postoperative analgesia, respiration, and hemodynamics in patients undergoing esophagectomy. METHODS In a randomized double-blind study, twenty patients undergoing esophageal cancer surgery with a thoracoabdominal procedure were studied. All patients received epidural morphine 2 mg at T6-7 and 2 mg at L3-4 at the beginning of wound closure. Then 3 ml/hr continuous epidural administration of either 0.25% bupivacaine (group Bup, 10 patients) or normal saline solution (group NS, 10 patients) through the catheter inserted at T6-7 was continued for 16 hours, followed by low-dose epidural buprenorphine-bupivacaine. RESULTS The time from end of operation to tracheal extubation was 4.4 +/- 6.7 hours in group Bup and 13.7 +/- 7.1 hours in group NS (p < 0.05). All patients in both groups obtained moderate or adequate pain relief (visual analog scale of 21 +/- 27 mm) without serious side effects. There were no significant differences in visual analog scale, score for pain on a deep breath, blood pressure, heart rate, or respiratory rate between the two groups. CONCLUSIONS Continuous administration of epidural bupivacaine combined with morphine resulted in good analgesia without any respiratory or hemodynamic depression in patients who had undergone esophagectomy, and early extubation is related to the efficacy of continuous epidural administration of bupivacaine.

Prostaglandin E1 as a hypotensive drug during general anesthesia for total hip replacement

STUDY OBJECTIVE To determine the effect of intravenous administration of prostaglandin E1 (PGE1) in inducing controlled hypotension during general anesthesia. DESIGN Randomized, prospective study. SETTING Inpatient surgery at a university hospital. PATIENTS 57 ASA physical status I and II patients scheduled for total hip replacement. INTERVENTIONS In 29 patients undergoing total hip replacement, PGE1 (0.11 +/- 0.03 micrograms/kg/min) was infused to induce hypotension during general anesthesia with enflurane, isoflurane, or sevoflurane in nitrous oxide and oxygen. In another 28 patients, the control group, normotensive anesthesia was performed for the same procedure. MEASUREMENTS AND MAIN RESULTS Systolic blood pressure decreased significantly (p < 0.01) from 136 +/- 22 mmHg to 93 +/- 10 mmHg during PGE1 infusion, although heart rate did not change significantly. Arterial hemoglobin oxygen saturation showed a mild but significant decrease (p < 0.05) during PGE1 infusion. Blood loss (480 +/- 132 ml) and blood transfusion (280 +/- 260 ml) during surgery were significantly less in patients with hypotensive anesthesia (p < 0.01 and p < 0.05, respectively) than in patients with normotensive anesthesia (667 +/- 326 ml and 468 +/- 395 ml, respectively). Blood loss and blood transfusion after surgery were similar in both groups. In the recovery room or surgical ward, 3 of 29 patients with hypotensive anesthesia needed rapid blood transfusion because of moderate hypotension. The volume of urine during surgery was significantly less (p < 0.05) in the control group. Two patients developed mild phlebitis at the site of the PGE1 infusion, but there were no serious side effects. CONCLUSION These data suggest that PGE1 can be used safely to induce hypotension, thereby reducing blood loss during total hip replacement with general anesthesia.

Device for determining location of an endotracheal catheter tip.

The location of a catheters tip in the bronchi may be determined using a stethoscope and an audible sound that has a frequency of 558 Hz and a sound pressure of 136 dB for the adult. The device is easy and safe to use, and has been used in a broad range of patients for over 4 yr without sequelae.

Effects of intravenous administration of local anesthetics on the renal sympathetic nerve activity during nitrous oxide and nitrous oxide‐halothane anesthesia in the cat

The effects of subseizure doses of lidocaine and bupivacaine administered intravenously (i.v.) on mean arterial pressure (MAP), heart rate (HR) and renal sympathetic nerve activity (RSNA) were studied in cats anesthetized with nitrous oxide (N2O)‐O2 and N2O‐O2‐halothane (1 %). In cats anesthetized with N2O‐O2, MAP decreased briefly (P<0.01) and then returned to the initial level within a minute after the i.v. injection of lidocaine (5 mg/kg, 10 mg/kg). RSNA increased at first and then decreased slightly. In cats with denervated baroreceptors, the change in RSNA after lidocaine 5 mg/kg i.v. was similar to that in cats with intact baroreceptors. In contrast, MAP, HR and RSNA decreased significantly (P<0.01) after i.v. injection of lidocaine during N2O‐O2‐halothane anesthesia. The effects of bupivacaine on RSNA were similar to those of lidocaine. It is concluded that cardiovascular depression following intravenous local anesthetics during N2O‐O2‐halothane anesthesia may be caused by both a decreased sympathetic activity and a direct depressant effect on the myocardium.

The effects of intrinsic nitric oxide on cardiac neural regulation in cats

In this study, we aimed to elucidate the effects of intrinsic nitric oxide (NO) on cardiac neural regulation.Twenty-two cats were anesthetized with 1.5% isoflurane and allocated to Group I (intact; n = 7), Group D (denervated baroreceptors and vagi; n = 8), or Group B (autonomic blockade with IV hexamethonium, propranolol, and atropine; n = 7). Cardiac sympathetic nerve activity (CSNA), mean arterial pressure (MAP), sinus heart rate (HR), and A-H and H-V intervals during pacing (150 bpm) were measured before and after IV administration of a NO synthase inhibitor, NG-nitro-L-arginine (L-NNA, 30 mg/kg) and after reversal with an excessive dose of L-arginine (300 mg/kg), before and during intermittent electrical stimulation of the posterior hypothalamus. L-NNA significantly increased MAP in Groups I and B, but not in Group D. L-NNA significantly decreased HR and lengthened A-H in Group I, but not in other groups. L-arginine further decreased HR and lengthened A-H unexpectedly. The reasons for these findings could not be determined in this study. L-NNA did not change CSNA. Hypothalamic stimulation did not potentiate L-NNA-induced changes in CSNA, hemodynamic variables, and atrioventricular conduction. In conclusion, intrinsic NO may modulate atrioventricular conduction and sinus rate through a vagal cholinergic, rather than a nonautonomic mechanism. Implications: Elucidating the roles of intrinsic nitric oxide (NO) on cardiac neural regulation is important. In intact, vagotomized, and baroreceptor-denervated or pharmacologically autonomic blockaded cats, an NO synthesis inhibitor was administered, and atrioventricular conduction and cardiac sympathetic neural discharge were measured. The results suggest a vagal cholinergic mechanism of intrinsic NO. (Anesth Analg 1998;86:1194-1200)

The monoethylglycinexylidide test is more useful for evaluating liver function than indocyanine green test: case of a patient with remarkably decreased indocyanine green half-life.

Lidocaine was used for evaluation of hepatic function in a patient undergoing hepatic resection. Preoperatively, half-life of indocyanine green (ICG) was 33 min after intravenous administration. Plasma concentration of the N-dealkylated metabolite of lidocaine, monoethylglycinexylidide (MEGX), was quantitatively determined to evaluate hepatic function. The patients rate of formation of MEGX at 15 min after administration of lidocaine was within normal limits, at 56 micrograms/L. These findings suggest that in this patient, hepatic cytochrome P-450IIIA activity was not impaired, but selective impairment of uptake of ICG into hepatocytes or excretion into the bile ducts was present. The rate of formation of MEGX was decreased, and plasma concentration of bilirubin was elevated postsurgically; this could have been the result of decreased cytochrome P-450IIIA activity or decreased hepatic blood flow after hepatic resection. We conclude that the rate of formation of MEGX is a better index of hepatic function than is ICG half-life.