Dexmedetomidine-induced atrioventricular block followed by cardiac arrest during atrial pacing: a case report and review of the literature.

Sinus bradycardia is a well-known consequence of stimulation of presynaptic α2 adrenergic receptors due the adminstration of dexmedetomidine. One of the most serious adverse effects of dexmedetomidine is cardiac arrest. Some cases demonstrating such an arrest due to the indiscriminate use of this drug were recently reported. We continuously administered dexmedetomidine to a 56-year-old male patient at a rate of 0.3 µg/kg/h (lower than the recommended dose) without initial dosing for sedation in an intensive care unit. The patient had undergone open cardiac surgery and atrial pacing was maintained at a fixed rate, 90/min. The PQ interval in electrocardiography gradually prolonged during the infusion; finally, complete atrioventricular block and subsequent cardiac arrest occurred. Immediate cardiopulmonary resuscitation was carried out, including re-intubation, and recovery of spontaneous circulation was attained 15 min after the event. The patient was discharged from hospital on the 25th postoperative day without any neurological complications.

The influence of endotoxemia on the electroencephalographic and antinociceptive effects of isoflurane in a swine model.

BACKGROUND: We have previously reported that hemorrhagic shock decreases the minimum alveolar anesthetic concentration (MAC) of isoflurane but minimally alters the electroencephalographic (EEG) effect. In this study, we investigated the influence of endotoxemia on the EEG effect and the MAC of isoflurane. METHODS: Eighteen swine (25.7 +/- 2.3 kg) were anesthetized by inhalation of isoflurane. The inhaled concentration was decreased to 0.5% and maintained for 20 min, before being returned to 2% and maintained for a further 20 min. End-tidal isoflurane concentrations and spectral edge frequencies were recorded. Analysis of the pharmacodynamics was performed using a sigmoidal inhibitory maximal effect model for spectral edge frequencies versus effect-site concentration. After measurement of the EEG effect, MAC was determined using the dewclaw clamp technique in which movement in response to clamping is recorded. After completion of control measurements, infusion of lipopolysaccharide (LPS, 1 microg x kg(-1) x h(-1)) was started after a 100-microg bolus administration. After 1 h, the inhaled concentration of isoflurane was varied as in the control period, and the MAC was assessed again (LPS1h). The same procedures were also performed after 3 h of LPS infusion (LPS3h). RESULTS: Endotoxemia decreased the effect-site concentration that produced 50% of the maximal effect from 1.31% +/- 0.22% to 1.13% +/- 0.14% (LPS1h) and 1.03% +/- 0.22% (LPS3h) and decreased the MAC from 2.05% +/- 0.20% to 1.51% +/- 0.30% (LPS1h) and 1.21% +/- 0.29% (LPS3h). CONCLUSIONS: Endotoxemia increases both the hypnotic and antinociceptive effects of isoflurane, in contrast to hemorrhagic shock, and the extent of these alterations increases with progression of endotoxemia.

Landiolol, an ultra short acting beta1-blocker, improves pulmonary edema after cardiopulmonary resuscitation with epinephrine in rats.

PURPOSE: Epinephrine is frequently administered as an essential drug for cardiopulmonary resuscitation (CPR) in clinical situations. Unfortunately, epinephrine elicits unfavorable effects, for example pulmonary edema, both during and after CPR. We hypothesized that administration of landiolol during CPR with epinephrine would reduce the degree of pulmonary edema and improve survival. Therefore using a rat CPR model, we investigated the effect of landiolol with epinephrine on pulmonary and cardiac injury following CPR. METHODS: Twelve male Sprague-Dawley rats were allocated to Group-E (Gr.-E: 0.02 mg/kg epinephrine) and thirteen animals to Group-EL (Gr.-EL: 0.02 mg/kg epinephrine with 0.5 mg/kg landiolol). After tracheotomy, cardiac arrest was induced by obstructing the endotracheal tube. We measured the lung wet-to-dry (W/D) weight ratio to evaluate the degree of pulmonary edema 2 h after CPR. The hematocrit (Hct) difference between before and after CPR (Hct-D) was calculated. We measured the plasma levels of troponin-I (T-I) to evaluate the degree of cardiac injury. RESULTS: The lung W/D weight ratio in Gr.-E (6.4 +/- 1.06, mean +/- SD) was significantly higher than that for Gr.-EL (4.9 +/- 0.80, p < 0.01). Hct-D was significantly higher in Gr.-E (10.2 +/- 3.1%) than in Gr.-EL (5.2 +/- 3.5%, p < 0.01). We observed no difference in survival or difference of T-I. (Gr.-E: 2.62 +/- 0.51 ng/ml, Gr.-EL: 3.43 +/- 2.72 ng/ml). CONCLUSION: Administration of landiolol during CPR with epinephrine prevented the development of pulmonary edema and the increase in Hct during and after CPR.

The influence of hemorrhagic shock on the electroencephalographic and immobilizing effects of propofol in a swine model.

BACKGROUND: Hemorrhagic shock increases the hypnotic effect of propofol, but the influence of hemorrhagic shock on the immobilizing effect of propofol is not fully defined. METHODS: Twenty-four swine (30.3 +/- 3.6 kg) were anesthetized by inhalation of isoflurane and randomly assigned to either a control (n = 12) or a hemorrhagic shock (n = 12) group. Animals in the shock group were bled to a mean arterial blood pressure of 50 mm Hg and maintained at this level for 60 min. After isoflurane inhalation was stopped, propofol was infused at 50 mg x kg(-1) x h(-1) until no movement was observed after application of a dewclaw clamp every 2 min. Arterial samples for measurement of the propofol concentration were collected just before each use of the dewclaw clamp and the Bispectral Index (BIS) was also recorded. Analysis of the pharmacodynamics was performed using a sigmoidal inhibitory maximal effect model for BIS versus effect-site concentration and a logistic regression analysis for the probability of movement versus effect-site concentration. RESULTS: The propofol doses needed to reach a 50% decrease from baseline BIS, and no movement after noxious stimuli were reduced by hemorrhagic shock by 54% and 38%, respectively. Hemorrhagic shock decreased the effect-site concentration that produced 50% of the maximal BIS effect from 11.6 +/- 3.8 to 9.1 +/- 1.7 microg/mL and that producing a 50% probability of movement from 26.8 +/- 1.0 to 20.6 +/- 1.0 microg/mL. CONCLUSIONS: The results show that hemorrhagic shock increases both the hypnotic and immobilizing effects of propofol due to pharmacokinetic and pharmacodynamic alterations, with the changes in pharmacodynamics occurring to a similar extent for both effects.

The influence of hemorrhagic shock on the minimum alveolar anesthetic concentration of isoflurane in a swine model.

BACKGROUND: Although hemorrhagic shock decreases the minimum alveolar concentration (MAC) of inhaled anesthetics, it minimally alters the electroencephalographic (EEG) effect. Hemorrhagic shock also induces the release of endorphins, which are naturally occurring opioids. We tested whether the release of such opioids might explain the decrease in MAC. METHODS: Using the dew claw-clamp technique in 11 swine, we determined the isoflurane MAC before hemorrhage, after removal of 30% of the estimated blood volume (21 mL/kg of blood over 30 min), after fluid resuscitation using a volume of hydroxyethylstarch equivalent to the blood withdrawn, and after IV administration of 0.1 mg/kg of the mu-opioid antagonist naloxone. RESULTS: Hemorrhagic shock decreased the isoflurane MAC from 2.05% +/- 0.28% to 1.50% +/- 0.51% (P = 0.0007). Fluid resuscitation did not reverse MAC (1.59% +/- 0.53%), but additional administration of naloxone restored it to control levels (1.96% +/- 0.26%). The MAC values decreased depending on the severity of the shock, but the alterations in hemodynamic variables and metabolic changes accompanying fluid resuscitation or naloxone administration did not explain the changes in MAC. CONCLUSIONS: Consistent with previous reports, we found that hemorrhagic shock decreases MAC. In addition, we found that naloxone administration reversed the effect on MAC, and we propose that activation of the endogenous opioid system accounts for the decrease in MAC during hemorrhagic shock. Such an activation would not be expected to materially alter the EEG, an expectation consistent with our previous finding that hemorrhagic shock minimally alters the EEG.

Landiolol, an ultra short-acting beta1-adrenoceptor antagonist, does not alter the minimum alveolar anesthetic concentration of isoflurane in a swine model.

BACKGROUND: We previously reported that landiolol, an ultra-short-acting beta1-adrenoceptor antagonist, does not alter the electroencephalographic effect of isoflurane. Here, we investigated the influence of landiolol on the minimum alveolar anesthetic concentration (MAC) of isoflurane required to prevent movement in response to a noxious stimulus in 50% of subjects. METHODS: Ten swine (29.0 +/- 3.4 kg) were anesthetized by inhalation of isoflurane. MAC was determined using the dewclaw clamp technique, in which movement in response to clamping is recorded. After determination of MAC in the baseline period, an infusion of landiolol (0.125 mg x kg(-1) x min(-1) for 1 min, then 0.04 mg x kg(-1) x min(-1)) was started. After a 20-min stabilization period, MAC was again assessed (0.04 mg x kg(-1) x min(-1) landiolol). The infusion of landiolol was then increased from 0.04 to 0.2 mg x kg(-1) x min(-1), and after a 20-min stabilization period, MAC was again assessed (0.2 mg x kg(-1) x min(-1) landiolol). Finally, the infusion of landiolol was stopped, and after a 20-min stabilization period, MAC was assessed for a fourth time (Baseline 2). RESULTS: Landiolol clearly attenuated the increases in heart rate and mean arterial blood pressure that occurred in response to the dewclaw clamp, but did not alter the MAC of isoflurane. CONCLUSIONS: Landiolol does not alter the antinociceptive effect of isoflurane. This result, combined with that from our previous work, also suggests that landiolol does not influence the anesthetic potency of inhaled anesthetics.

Is the ipsilateral cortex surrounding the lesion or the non-injured contralateral cortex important for motor recovery in rats with photochemically induced cortical lesions?

PRIMARY OBJECTIVE: To determine whether the ipsilateral cortex surrounding the lesion or the non-injured contralateral cortex is important for motor recovery after brain damage in the photochemically initiated thrombosis (PIT) model. RESEARCH DESIGN: We induced PIT in the sensorimotor cortex in rats and examined the recovery of motor function using the beam-walking test. METHODS AND PROCEDURES: In 24 rats, the right sensorimotor cortex was lesioned after 2 days of training for the beam-walking test (group 1). After 10 days, PIT was induced in the left sensorimotor cortex. Eight additional rats (group 2) received 2 days training in beam walking, then underwent the beam-walking test to evaluate function. After 10 days of testing, the left sensorimotor cortex was lesioned and recovery was monitored by the beam-walking test for 8 days. MAIN OUTCOMES AND RESULTS: In group 1 animals, left hindlimb function caused by a right sensorimotor cortex lesion recovered within 10 days after the operation. Right hindlimb function caused by the left-side lesion recovered within 6 days. In group 2, right hindlimb function caused by induction of the left-side lesion after a total of 12 days of beam-walking training and testing recovered within 6 days as with the double PIT model. The training effect may be relevant to reorganization and neuromodulation. Motor recovery patterns did not indicate whether motor recovery was dependent on the ipsilateral cortex surrounding the lesion or the cortex of the contralateral side. CONCLUSION: The results emphasize the need for selection of appropriate programs tailored to the area of cortical damage in order to enhance motor functional recovery in this model.

Influence of hemorrhagic shock and subsequent fluid resuscitation on the electroencephalographic effect of isoflurane in a swine model.

BACKGROUND: The authors have previously reported that hemorrhage does not alter the electroencephalographic effect of isoflurane under conditions of compensated hemorrhagic shock. Here, they have investigated the influence of decompensated hemorrhagic shock and subsequent fluid resuscitation on the electroencephalographic effect of isoflurane. METHODS: Twelve swine were anesthetized through inhalation of 2% isoflurane. The inhalational concentration was then decreased to 0.5% and maintained for 25 min, before being returned to 2% and maintained for 25 min (control period). Hemorrhagic shock was then induced by removing 28 ml/kg blood over 30 min. After a 30-min stabilization period, the inhalational concentration was varied as in the control period. Finally, fluid infusion was performed over 30 min using a volume of hydroxyethyl starch equivalent to the blood withdrawn. After a 30-min stabilization period, the inhalational concentration was again varied as in the control period. End-tidal isoflurane concentrations and spectral edge frequency were recorded throughout the study. The pharmacodynamics were characterized using a sigmoidal inhibitory maximal effect model for spectral edge frequency versus effect site concentration. RESULTS: Decompensated hemorrhagic shock slightly but significantly shifted the concentration-effect relation to the left, demonstrating a 1.12-fold decrease in the effect site concentration required to achieve 50% of the maximal effect in the spectral edge frequency. Fluid resuscitation reversed the onset of isoflurane, which was delayed by hemorrhage, but did not reverse the increase in end-organ sensitivity. CONCLUSIONS: Although decompensated hemorrhagic shock altered the electroencephalographic effect of isoflurane regardless of fluid resuscitation, the change seemed to be minimal, in contrast to several intravenous anesthetics.

Influence of hypovolemia on the electroencephalographic effect of isoflurane in a swine model.

BACKGROUND: Hypovolemia alters the effect of several intravenous anesthetics by influencing pharmacokinetics and end-organ sensitivity. The authors investigated the influence of hypovolemia on the effect of an inhalation anesthetic, isoflurane, in a swine hemorrhage model. METHODS: Eleven swine were studied. After animal preparation with inhalation of 2% isoflurane anesthesia, the inhalation concentration was decreased to 0.5% and maintained at this level for 25 min before being returned to 2% (control). After 25 min, hypovolemia was induced by removing 14 ml/kg of the initial blood volume via an arterial catheter. After a 25-min stabilization period, the inhalation concentration was decreased to 0.5%, maintained at this level for 25 min, and then returned to 2% (20% bleeding). After another 25 min, a further 7 ml/kg blood was collected, and the inhalation concentration was altered as before (30% bleeding). End-tidal isoflurane concentrations and an electroencephalogram were recorded throughout the study. Spectral edge frequency was used as a measure of the isoflurane effect, and pharmacodynamics were characterized using a sigmoidal inhibitory maximal effect model for the spectral edge frequency versus end-tidal concentration. RESULTS: There was no significant difference in the effect of isoflurane among the conditions used. Hypovolemia did not shift the concentration-effect relation (the effect site concentration that produced 50% of the maximal effect was 1.2 +/- 0.2% under control conditions, 1.2 +/- 0.2% with 20% bleeding, and 1.1 +/- 0.2% with 30% bleeding). CONCLUSIONS: Hypovolemia does not alter the electroencephalographic effect of isoflurane, in contrast to several intravenous anesthetics.

Influence of fluid infusion associated with high-volume blood loss on plasma propofol concentrations.

BACKGROUND: It is common clinical practice to use fluid infusion to manage high-volume blood loss until a blood transfusion is performed. The authors investigated the influence of fluid infusion associated with blood loss on the pseudo-steady state propofol concentration. METHODS: Twenty-seven swine were assigned to a lactated Ringer's solution group, a hydroxyethyl starch group, or a threefold lactated Ringer's solution group (n = 9 in each group). After 180 min of steady state infusion of propofol at a rate of 2 mg.kg(-1).h(-1), hemorrhage and infusion were induced by stepwise bleeding followed by fluid infusion every 30 min. In each of the first two steps, 400 ml blood was collected; thereafter, 200 ml was collected at each step. Just after each bleeding step, fluid infusion was rapidly performed using a volume of lactated Ringer's solution or hydroxyethyl starch equivalent to the blood withdrawn, or a threefold volume of lactated Ringer's solution. Hemodynamic parameters and the plasma propofol concentration were recorded at each step. RESULTS: Although the plasma propofol concentration in the lactated Ringer's solution group increased with hemorrhage and infusion, it decreased in both the hydroxyethyl starch and the threefold lactated Ringer's solution groups. The propofol concentration in the hydroxyethyl starch group could be expressed by the following equation: Plasma Propofol Concentration Decrease (%) = 0.80 x Hematocrit Decrease (%) (r2 = 0.83, P < 0.0001). CONCLUSIONS: When high-volume blood loss is managed by isovolemic hemodilution, the plasma propofol concentration during continuous propofol infusion decreases linearly with the hematocrit decrease.