Nobutaka Kariya

Oral clonidine for sedation and analgesia in a burn patient

Clonidine has both analgesic and sedative actions, and it has been used in a variety of settings as a sedative, or both. We administered oral clonidine with intravenous ketamine to a burn patient to control severe pain. Clonidine produced good analgesia and sedation. In addition, clonidine counterbalanced the sympathetic stimulation of ketamine by virtue of its action in reducing sympathetic outflow. The combination of these two drugs may be useful for burn patients with hypertension or myocardial ischemia.

Bupivacaine-induced QRS prolongation is enhanced by lidocaine and by phenytoin in rabbit hearts.

UNLABELLED Lidocaine, phenytoin, and bupivacaine are sodium channel blockers. Lidocaine displaces bupivacaine from its receptor on the sodium channel. However, lidocaine does not seem to decrease bupivacaine toxicity. Phenytoin also has been used to treat bupivacaine cardiotoxicity. To test the hypothesis that lidocaine or phenytoin might be used for the treatment of bupivacaine overdose, we compared the effects of bupivacaine on intraventricular conduction in the isolated heart of rabbits with bupivacaine and with either phenytoin or lidocaine added to bupivacaine. Twenty-four rabbit hearts were retrogradely perfused in a nonrecirculating Langendorff apparatus. The duration of QRS was measured without any drug and 10 min after infusion of 3 microM bupivacaine. Saline (control group) or increasing concentrations of either lidocaine or phenytoin was then added by 10-min-step increments. QRS duration was measured for each concentration at the end of a 10-min step. It was also determined 10 min after discontinuation of bupivacaine and after a period of washout for all drugs. QRS duration was significantly increased by adding phenytoin or lidocaine to bupivacaine. These drugs should not be used to treat the manifestations of bupivacaine toxicity. IMPLICATIONS The effects of lidocaine and phenytoin on bupivacaine-related increases in cardiac conduction time have been studied in an isolated heart preparation. Both drugs increased the QRS widening induced by bupivacaine. We conclude that none of these drugs should be used for treating bupivacaine intoxication.

Effect of bupivacaine on the isolated rabbit heart: Developmental aspect on ventricular conduction and contractility

Background:Newborns and infants seem to be at greater risk of bupivacaine cardiotoxicity than adults do. Few experiments have studied the effects of local anesthetics on myocardium associated with developmental changes, and their conclusions are conflicting. The authors compared the effects of bupivacaine on an isolated heart preparation in newborn and adult rabbits. Methods:The authors used a constant-flow, nonrecirculating Langendorff preparation paced atrially. Adult and newborn rabbit hearts were exposed to step-increasing concentrations of bupivacaine. For each concentration, heart rate was modified with pacing from 180 to 360 beats/min by increments of 30 beats/min. QRS complex duration (index of ventricular conduction) and the first derivative of left ventricular pressure (index of contractility) were measured. The two groups were compared using an Emax model. Results:In newborn and adult rabbits, QRS complex duration increased with increasing bupivacaine concentration. No difference was observed between neonatal and adult hearts. Contractility decreased with increasing bupivacaine concentration. Newborn rabbits were approximately three times more sensitive than adult rabbits to the effects of bupivacaine. However, the concentration leading to 50% decrease in the first derivative of left ventricular pressure was much higher than the concentration leading to half maximum increase in QRS complex duration. Conclusions:In conclusion, using a whole organ preparation, the authors demonstrated that bupivacaine induces similar impairment in ventricular conduction in newborn and adult rabbits. In particular, the tonic and the phasic blocks were of similar intensity in both groups. Conversely, the effect of bupivacaine on contractility was markedly higher in newborn rabbits than in adult rabbits. Also, contractility was less impaired than ventricular conduction in both groups.

Coronary Artery Spasm Induced by Trigeminal Nerve Stimulation and Vagal Reflex During Intracranial Operation

This report describes a case of ventricular fibrillation resulting from coronary vasospasm during intracranial operation under general anesthesia. An autonomic response associated with the intracranial procedure caused a coronary spasm, which was worsened by alpha-agonists. Nitroglycerin effectively resolved the coronary spasm and co-complications persisted.

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.

The use of intravenous nitroglycerin in a case of spasm of the sphincter of Oddi during laparoscopic cholecystectomy.

Spasm of the sphincter of Oddi still occurs during cholecystectomy. Some reports indicate that the spasm, induced by morphine, can be reversed by injection of naloxone, nalbuphine, and glucagon. Others maintain that nitroglycerin or nifedipine can relax the sphincter of Oddi muscle. We recently encountered spasm of the sphincter of Oddi during a laparoscopic cholecystectomy and treated it successfully with intravenous nitroglycerin.

Electrocardiographic artifacts during shoulder arthroscopy using a pressure-controlled irrigation pump.

E lectrocardiographic interference which mimics cardiac arrhythmias is reportedly caused by a variety of medical equipment (1–4). Recently, we encountered puzzling baseline electrocardiographic artifacts that simulated atrial flutter or atrial fibrillation during shoulder arthroscopy using a pressurecontrolled irrigation pump (Fig. 1). We concluded that a new technique or equipment using a roller pump can create electrocardiographic artifacts that can mimic atrial flutter or atrial fibrillation.

The pharmacokinetic change of lidocaine by catecholamines using isolated perfused rat liver (IPRL)

We hypothesized that changes in the pharmacokinetics of lidocaine might reveal changes in portal circulation induced by catecholamines. Isolated perfused rat liver (IPRL) was selected as an experimental model, since experimental conditions in this model could be regulated. The liver was perfused with a recirculating system at a constant flow rate of 20 ml/min. Two milligrams of lidocaine was administered along with one of three drugs, dopamine, norepinephrine or adenosine triphosphate. The fractional transfer rate constants, k21 and k12, from medium to liver and liver to medium, respectively, and ke, the elimination rate constant, were calculated using a two-compartment model with the SAAM II program. Curves of decay of lidocaine from the recirculating medium consisted of a fast and a slow component. Norepinephrine and high-dose dopamine significantly increased k12, while low-dose dopamine significantly increased k21 and ke compared with control values. Thus, norepinephrine and high-dose dopamine increased lidocaine transfer rate from liver to medium, while low-dose dopamine increased the transfer rate from medium to liver and the rate of elimination from liver. These findings suggest that norepinephrine and high-dose dopamine inhibit hepatic drug uptake and that low-dose dopamine improves uptake in IPRL.

A case of fatal paradoxical fat embolism syndrome detected by intraoperative transesophageal echocardiography.

A 30-yr-old male truck driver with no history of cardiac or cerebral disease was admitted to the intensive care unit after his truck was struck by another truck from behind, and the dashboard trapped him. On arrival, he had no apparent neurological deficit, with normal findings on brain computed tomography (CT). Tachypnea (36 breaths/min), tachycardia (81 bpm), and hypercapnia (Paco2: 55.0 mm Hg) with normal oxygenation and normal arterial blood pressure were observed. Surgery was performed to fixate the closed fractures of the right femoral shaft fracture with intramedullary nails (with 12-mm diameter and 38-cm length) during general anesthesia. Approximately 90 min after starting the operation, a decreased end-tidal CO2 and oxygen saturation (Spo2) occurred followed by hypercapnia, hypoxia, tachycardia, hypotension, and pulmonary hypertension (pulmonary artery pressure was 46/29 mm Hg). TEE revealed multiple small vesicles in all four heart chambers (Fig. 1), marked pulmonary artery dilation, and depression of contraction of the right ventricle. PFES was strongly suspected, and the operation was completed as quickly as possible. Postoperatively, the patient remained in a coma. Brain CT findings were almost the same as those of preoperative examination both immediately after, and 3 h after, the operation. However, there was severe global edema in both cerebral hemispheres at 8 h after the operation. After hypothermic therapy with a blood temperature of 34°C for 3 days, the patient remained in a coma; cerebral edema was observed on brain CT, which did not improve. Contrast TEE using plasma protein fraction revealed the appearance of microbubbles in both atria almost simultaneously. However, the location of the shunt was not identified by color Doppler echocardiography. Phagocytosis of fat vesicles by macrophages was also demonstrated in both pulmonary and arterial blood samples (Fig. 2) and a bronchoalveolar lavage fluid sample. The patient died on the ninth hospital day of severe hypotension caused by brain herniation. The request to perform an autopsy was denied by his family.

The effects of norepinephrine and prostaglandin E1 on pharmacokinetics of lidocaine in isolated perfused rat liver.

We hypothesized that depression of liver function by norepinephrine can be improved by prostaglandin E1. Isolated perfused rat liver was selected as an experimental model, since the flow rate can be regulated in it. Twenty-one rats were randomly allocated to three groups: control, norepinephrine, and norepinephrine and prostaglandin E1 groups. The liver was perfused in a recirculating system at a constant flow rate of 20 ml/min. After administration of two milligrams of lidocaine in each group, lidocaine and monoethylglycinexylidide concentrations in the recirculating system were measured. Lidocaine pharmacokinetics were analyzed using the SAAM II program, including metabolic rate from lidocaine to monoethylglycinexylidide using time-concentration curves. Norepinephrine significantly increased perfusion pressure and the area under the time-concentration curve for lidocaine. Norepinephrine decreased the clearance and the elimination rate constant of lidocaine compared with those in the control group. Although administration of prostaglandin E1 after infusion of norepinephrine did not significantly change perfusion pressure, it significantly (p < 0.05) improved metabolic rate, clearance and the elimination rate constant of lidocaine in the isolated rat liver model.