Biomedical subjects

C M Bernards

Publications and source records attributed to C M Bernards.

43 records · Page 3Linked to original sources

PubMed1991

Hexamethonium and midazolam terminate dysrhythmias and hypertension caused by intracerebroventricular bupivacaine in rabbits.

Previous studies have demonstrated that bupivacaine administered directly into the central nervous system (CNS) is capable of producing signs of bupivacaine cardiovascular toxicity. To investigate the mechanisms by which bupivacaine may act within the CNS to produce cardiovascular toxicity, we studied four groups of halothane-anesthetized rabbits in which infusion of intracerebroventricular (icv) bupivacaine or intravenous (iv) phenylephrine resulted in dysrhythmias and hypertension. In group 1 (n = 5), icv bupivacaine (500 +/- 79 micrograms [mean +/- SEM]) produced dysrhythmias lasting 73 +/- 13 min, whereas icv saline caused no dysrhythmias or hypertension. In group 2 (n = 9), icv bupivacaine-induced hypertension and dysrhythmias were abolished by icv midazolam in 4.4 +/- 0.6 min, and when dysrhythmias and hypertension recurred (22 +/- 0.9 min), hexamethonium (10 mg/kg iv) promptly terminated dysrhythmias and hypertension (14 +/- 1 s). In group 3 (n = 10), icv bupivacaine-induced dysrhythmias and hypertension were not affected by increasing the inspired halothane concentration from 0.8 to 1.6%. In group 4 (n = 6), iv phenylephrine-induced dysrhythmias and hypertension were not affected by icv midazolam. These results suggest that icv bupivacaine produces dysrhythmias and hypertension by increasing autonomic nervous system (ANS) outflow from the brain stem. The finding that peripheral autonomic blockade by hexamethonium rapidly terminated dysrhythmias and hypertension supports this mechanism. We speculate that icv bupivacaine produces an increase in autonomic outflow by blockade of the inhibitory gamma-aminobutyric acid (GABA) neurons that are known to be the principal tonic inhibitors of the ANS.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

The spinal nerve root sleeve is not a preferred route for redistribution of drugs from the epidural space to the spinal cord.

It has been frequently suggested that the spinal nerve root sleeve is a preferred route for redistribution of drugs from the epidural space to the spinal cord. To determine if this supposition is true, the authors measured the rate at which morphine, fentanyl, and lidocaine diffuse through dog and monkey meningeal specimens with and without a root sleeve. Two meningeal specimens of intact dura-arachnoid-pia mater were removed from each animal and placed in separate temperature-controlled diffusion cells. One specimen included a spinal nerve root sleeve; the other did not. The permeability of the tissues to each drug was then determined by placing the study drug in one of the reservoirs of the diffusion cell and measuring the rate at which the drug diffused through the tissue and accumulated in the second reservoir. There was no difference in permeability between specimens with and without a nerve root sleeve for any drug in either species. Lidocaine was found to diffuse through the tissue significantly faster than fentanyl in both the dog and monkey even though fentanyl is nearly 48 times more lipid soluble than lidocaine. Morphine diffused through the tissue significantly slower than both lidocaine and fentanyl. The authors conclude that the spinal nerve root sleeve is not a preferred route of entry for drugs moving from the epidural space to the spinal cord. In addition, despite hypotheses to the contrary, lipid solubility does not appear to be the overriding determinant of meningeal permeability.

Animals↗

PubMed1990

Morphine and alfentanil permeability through the spinal dura, arachnoid, and pia mater of dogs and monkeys.

Little information exists about which spinal meninx is the principal permeability barrier between the epidural space and the spinal cord or about what physicochemical properties of drug molecules govern their meningeal permeability. To better understand these aspects of epidural pharmacokinetics, the authors measured the permeability of morphine and alfentanil through the different components of the spinal meninges-dura mater, arachnoid mater, and pia mater-of dogs and monkeys in vitro. Live meningeal tissue from either species (dura mater alone, pia mater alone, or intact dura-arachnoid-pia) was placed between two fluid reservoirs of a temperature-controlled diffusion cell. The permeability of the tissues to each opioid was determined by placing the opioid in one of the reservoirs of the diffusion cell and measuring the rate at which the drug diffused through the tissue and appeared in the second reservoir. The arachnoid mater was found to be the major meningeal diffusion barrier between the epidural space and the spinal cord. Alfentanil was 3.7 times more permeable than morphine through all three meninges, suggesting that increased lipid solubility increases meningeal permeability. However, neither lipid solubility nor molecular weight adequately explained the difference in permeability between morphine and alfentanil. The authors conclude that this in vitro model has significant utility for studies aimed at predicting in vivo meningeal permeability and hence the potency and rapidity of action of any opioid administered by the epidural route.

Alfentanil↗

PubMed1989

Effect of midazolam and diazepam premedication on central nervous system and cardiovascular toxicity of bupivacaine in pigs.

To determine the effect of benzodiazepine premedication on central nervous system and cardiovascular effects of bupivacaine, the authors administered toxic doses of bupivacaine to awake spontaneously breathing pigs after intravenous premedication with midazolam (0.06 mg/kg), diazepam (0.15 mg/kg), or saline. Five minutes after administration of one of these solutions, they began an infusion of bupivacaine at 2 mg.kg-1.min-1. The bupivacaine infusion was continued until cardiovascular collapse. They then attempted to resuscitate the animals via open chest cardiac massage and a standard resuscitation protocol. Premedication with midazolam or diazepam significantly delayed the onset of ventricular dysrhythmias (P less than 0.05), decreased the incidence of seizures (P less than 0.05), and prevented the increase in blood pressure and heart rate following bupivacaine infusion (P less than 0.05). Benzodiazepine premedication did not affect the dose of bupivacaine or the blood concentration required to produce cardiovascular collapse. The ability to resuscitate animals premedicated with midazolam did not differ from control; however, significantly fewer animals premedicated with diazepam were resuscitated (P less than 0.05). A clinically relevant observation was that almost all animals premedicated with a benzodiazepine progressed directly to cardiovascular collapse without first manifesting seizures.

Animals↗

PubMed1989

Effect of epinephrine on central nervous system and cardiovascular system toxicity of bupivacaine in pigs.

To determine what effect the addition of epinephrine has on bupivacaine toxicity, toxic doses of bupivacaine were administered to awake spontaneously breathing pigs. Twenty animals were randomized to one of two groups. One group received an infusion of bupivacaine with epinephrine (5 micrograms/ml) at a rate of 2 mg.kg-1.min-1; the other received an infusion of plain bupivacaine at the same rate. Bupivacaine infusion was continued until cardiovascular collapse. Following cardiovascular collapse we attempted to resuscitate the animals via open chest cardiac massage and a standardized resuscitation protocol. The addition of epinephrine to bupivacaine significantly increased blood pressure and systemic vascular resistance but not heart rate or cardiac output early in the bupivacaine infusion. Epinephrine had no effect on the dose of bupivacaine that caused cardiovascular collapse (P = 0.1), on the plasma concentration of bupivacaine at collapse (P = 0.9), or on the ability to resuscitate animals following cardiovascular collapse. The addition of epinephrine decreased the dose of bupivacaine required to initiate cardiac dysrhythmias (P = 0.003). The first dysrhythmia experienced by the epinephrine group was second degree heart block, which contrasts with the premature ventricular and atrial dysrhythmias experienced by the plain group. The dose of bupivacaine that produced seizures was also reduced by the addition of epinephrine (P = 0.006). The addition of epinephrine to bupivacaine did not alter the dose of bupivacaine that caused cardiovascular collapse in awake spontaneously breathing pigs but did decrease the dose of bupivacaine that caused seizures and dysrhythmias.

Animals↗

PubMed1988

Intrathecal morphine reduces the minimum alveolar concentration of halothane in humans.

The authors hypothesized that the analgesia provided by intraspinal opiates would decrease anesthetic requirement. To test this hypothesis, 20 women undergoing major gynecologic surgery were divided randomly into two groups. One group received 0.75 mg morphine sulfate intrathecally, and the other, the same dose intramuscularly (control), prior to the induction of anesthesia with halothane. MAC for halothane was 0.81% in the control group and 0.46% in the intrathecal morphine group (P = 0.024). The reduction in anesthetic requirement due to intrathecal morphine is greater than that produced by low to moderate doses of systemically administered opiates.

Anesthesia, Inhalation↗

PubMedDate not supplied

Effect of Staphylococcus aureus bacteria and bacterial toxins on meningeal permeability in vitro.

BACKGROUND AND OBJECTIVES: Epidural catheterization is associated with a significant bacterial colonization rate and occasionally frank infection. During epidural space infection, decreased analgesia despite increased epidural opioid doses has been described. One possible explanation for this observation is that bacterial infection decreases meningeal permeability. The purpose of the study was to determine whether Staphylococcus aureus bacteria, the most common organism causing epidural space infection, or S. aureus toxins alter meningeal permeability. METHODS: Spinal meninges of M. nemestrina monkeys were mounted in a previously established in vitro diffusion cell model and exposed to S. aureus toxins A, B, and F. Simultaneous transmeningeal fluxes of mannitol and sufentanil were measured before and after toxin exposure and compared to controls. In a second series of experiments, diffusion cells were inoculated with live S. aureus bacteria in suspension and the permeability of sufentanil was investigated. RESULTS: Staphylococcus aureus toxin-A increased the transmeningeal flux of mannitol but not sufentanil. Toxins B and F did not alter the meningeal permeability of either drug. Inoculation with live S. aureus bacteria increased the transmeningeal flux of sufentanil by 115+/-21% (P = .032). CONCLUSIONS: These data demonstrate that S. aureus alpha-toxin and live S. aureus bacteria can increase meningeal permeability. Thus, clinical observations of decreased epidural analgesia in the face of bacterial infection cannot be explained by decreased meningeal permeability.

Animals↗