John Hartung

Midazolam Enhances Anterograde but not Retrograde Amnesia in Pediatric Patients

BackgroundMidazolam sedation has been shown to diminish recall of one to four cards shown prior to induction of general anesthesia in pediatric patients. This promising but limited finding prompted us to investigate the effect of midazolam sedation on retrograde and anterograde recall and recognition in children scheduled for elective surgery. MethodsForty patients aged 4–10 yr were randomized using a double-blind study design to receive either 0.2 mg/kg intranasal midazolam or 0.2 ml/5 kg placebo (distilled water) using a Devilbiss #286 atomizer. To assess postoperative memory of preoperative events, recall and recognition tasks were performed using a series of picture cards designed for this purpose. Retrograde amnesia was measured by postoperative recall and recognition of cards shown prior to midazolam/placebo administration, and anterograde amnesia was measured by postoperative recall and recognition of cards shown during the interval between midazolam/placebo administration and induction of general anesthesia. ResultsCompared to placebo, the midazolam group experienced a significant postoperative reduction in ability to both recall (P <.003) and recognize (P <.001) cards shown subsequent to midazolam/placebo administration (anterograde amnesia). In distinction, there was no difference between groups in postoperative ability to recall or recognize cards shown prior to midazolam/placebo administration (retrograde amnesia). ConclusionsThese results support and extend the inference that midazolam diminishes anterograde recall. In addition, our findings indicate that midazolam diminishes anterograde recognition, thereby providing partial anterograde amnesia without affecting retrograde memory in pediatric patients.

Twenty-Four of Twenty-Seven Studies Show a Greater Incidence of Emesis Associated with Nitrous Oxide than with Alternative Anesthetics

All obtainable investigations that have compared the incidence of vomiting in groups of patients who received nitrous oxide (N2 O) and in patients who received anesthetics or analgesics without N2 O were examined for a single, dichotomous variable:whether patients who received N2 O experienced an absolutely higher incidence, as distinct from a statistically significantly higher incidence, of vomiting. The null hypothesis is that N2 O has no effect on emesis, such that an increased incidence of vomiting should occur in about half of the studies examined. However, patients receiving N2 O experienced an absolutely higher incidence of emesis in 24 of 27 investigations. The two-tailed probability that this result occurred by chance is <0.00005. It follows that N2 O increases the incidence of emesis compared to alternative anesthetics. (Anesth Analg 1996;83:114-6)

Intracranial and Hemodynamic Changes after Succinylcholine Administration in Cats

Bolus injections of succinylcholine (1.5 mg/kg) significantly increased intracranial pressure (ICP) in cats under normal conditions from control levels of 8 ± 1 mm Hg to 16 ± 3 mm Hg (± SEM, P < 0.01), and in the presence of artificially increased ICP from control levels of 27 ± 1 mm Hg to 47 ± 4 mm Hg (P < 0.01). These approximately 100% increases in ICP were accompanied by a transitory decrease in mean arterial pressure (approximately 10 sec), followed by a 15–20% increase (P < 0.05). Pulmonary arterial pressure increased 20–30% (P < 0.05). These results, when considered in conjunction with results previously obtained in humans, suggest that succinylcholine may be contraindicated in neurosurgical patients.

Nitrous Oxide Increases Intraocular Pressure after Intravitreal Sulfur Hexafluoride Injection

In anesthetized cats ventilated with oxygen, 0.5 ml of the inert gas sulfur hexafluoride (SF6) was substituted for vitreous. When the ventilating gas was changed to nitrous oxide (N2O) 66%, balance oxygen, intraocular pressure increased from 14.4 to 30.3 mmHg in 19.5 min. When the ventilating gas was changed back to oxygen, intraocular pressure decreased from 29.1 to 12.0 mmHg in 18.1 min. This intraocular pressure change secondary to gas volume alteration may adversely affect therapeutic outcome of ophthalmic surgery. Accordingly, N2O should be avoided in patients during and following intravitreal injection of SF6 for up to 10 days.

Intracranial pressure during nifedipine-induced hypotension.

The effect of nifedipine-induced hypotension on intracranial pressure (ICP) was investigated in cats with normal and artificially increased ICP. Eleven cats were anesthetized with intraperitoneal pentobarbital (25 mg/kg), intubated, and ventilated with nitrous oxide in oxygen. Mean arterial pressure (MAP), heart rate (HR), and mean pulmonary artery pressure (PAP) were continuously recorded. A double 19-gauge needle was inserted into the cisterna magna; ICP was continuously monitored from one needle and the other was used to increase and maintain ICP at 27 ± 4 mm Hg by infusion of pH-adjusted Ringers lactate solution. After control measurements were taken, nifedipine was given intravenously in each cat when ICP was normal and increased. Infusion of 96 ± 12 μg (SEM) nifedipine (≅33 μg/kg) reduced MAP 35–45% for 2.5 ± 0.8 min when ICP was normal, and for 2.0 ± 0.6 min when ICP had been increased. When initial ICP was normal, nifedipine-induced hypotension produced a small (2.2 mm Hg) but statistically significant increase in ICP and decrease in cerebral perfusion pressure (P < 0.01). When ICP was initially elevated, nifedipine-induced hypotension produced a larger increase in ICP (5 ± 1 mm Hg) and a proportionately larger decrease in cerebral perfusion pressure (P < 0.01).

Nitrous oxide reduces thiopental-induced prolongation of survival in hypoxic and anoxic mice.

Arnfreds mouse model urns used to test the effect of thiopental during hypoxia (5% O2) and anoxia, with and without simultaneous administration of nitrous oxide. As found by Arnfred and others, thiopental without N2O more than doubled survival time during hypoxia (from 5.2 ± 0.6 to 13.9 ± 2.6 min). This effect was completely offset by simultaneous use of N2O (from 13.9 ± 2.6 to 4.8 ± 0.7 min). Thiopental without N2O also increased survival time during complete anoxia (from 26 ± 1 to 59 ± 1 sec). This effect was diminished by 58% when N2O was added (from 59 ± 1 to 40 ± 1 sec). We conclude that nitrous oxide diminishes the effect of barbiturates upon survival time in hypoxic and anoxic mice.

Propofol prevents or elevates the threshold for lidocaine-induced seizures in rats.

Hypothesizing that propofols pro and anticonvulsant effects might be dose dependent, we determined the effect of 25, 50, and 100% of a previously determined anesthetic dose of propofol for rats on the amount of lidocaine required to induce seizures. Lidocaine was infused at 2.5 mg kg-1 min-1 into animals that were receiving either (a) 70% N2O balance O2 (n = 10), control group, (b) 2 mg kg-1 bolus followed by 12 mg kg-1 h-1 propofol infusion with 70% N2O (n = 10), group 2, (c) 4 mg kg-1 followed by 24 mg kg-1 h-1 propofol with 70% N2O (n = 20), group 3, (d) 8 mg kg-1 followed by 48 mg kg-1 h-1 propofol with 70% N2O (n = 10), group 4, or (e) 8 mg kg-1 followed by 48 mg kg-1 h-1 propofol without N2O (n = 10), group 5. Temperature PaCO2, and pH were maintained within normal limits until disturbed by seizure activity or lidocaine toxicity. The plasma concentration of lidocaine required to induce electroencephalographically (EEG) detected seizures was 8.7 +/- 0.7 micrograms ml-1 in control animals, 16 +/- 1.7 micrograms ml-1 in group 2, and 32 +/- 4 micrograms ml-1 in 13 animals from group 3 that experienced a seizure (p < 0.01). Seizures did not occur in seven of 20 group 3 rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Intracranial Pressure During Diltiazem-induced Hypotension in Anesthetized Dogs

The effect of diltiazem-induced hypotension on intracranial pressure (ICP) was studied in dogs with normal and elevated ICP. Eight dogs were anesthetized with intravenous pentobarbital, intubated, and ventilated with N2O:O2. Mean arterial pressure (MAP), heart rate (HR), pulmonary artery pressure (PAP), pulmonary capillary wedge pressure (PCWP), central venous pressure (CVP), and cardiac output (CO) were recorded. A ventriculostomy was performed for measurement of ICP. Baselines were established, and diltiazem was infused to reduce MAP 40 ± 1% for 10 min. After recording the effects of diltiazem-induced hypotension during normal ICP, ICP was elevated by infusion through a ventriculostomy cannula of pH-adjusted Ringers lactate, baselines were reestablished, and MAP was again reduced by 40 ± 1% with diltiazem. When baseline ICP was normal, diltiazem-induced hypotension produced a statistically significant increase in ICP (4.8 ± 0.6 mm Hg) and a decrease in cerebral perfusion pressure (CPP). When baseline ICP was elevated, a smaller increase in ICP occurred (1.3 ± 0.5 mm Hg). Although these increases in ICP were not clinically significant, the dose of diltiazem required to lower MAP 40% caused significant alterations in HR, systemic vascular resistance, CO, and PCWP. Serious cardiac rhythm disturbances occurred in five of eight dogs when baseline ICP was normal and in six of eight dogs when baseline ICP was elevated. The relatively long duration of diltiazems hemodynamic effect and the high incidence of cardiac rhythm disturbances make it an unsuitable drug for inducing deliberate hypotension.

Intracranial pressure mean arterial pressure and heart rate after rapid paralysis with atracurium in cats.

The effect of atracurium on intracranial pressure (ICP) was investigated in six cats with normal and increased ICP. The cats were anaesthetized with intraperitoneal pentobarbitone (33mg·kg-1), acepromazine (0.6mg·kg-1) and incremental fentanyl (p.r.n.≅ 20μg·kg-1), intubated, and ventilated with nitrous oxide in oxygen. Mean arterial pressure (MAP), heart rate (HR), twitch response and ICP were continuously recorded. After the effect of atracurium had been ascertained under the condition of normal ICP, and after full recovery of twitch response, pH-adjusted Ringer’s lactate solution was infused into the cisterna magna until an ICP baseline of 26 ±2 mmHg was established and stabilized. Atracurium was then administered again to determine its effect under the condition of elevated ICP. Complete ablation of twitch response was obtained in 68 ± 15 sec with 0.4 mg·kg-1 atracurium, and there was no significant change in ICP, MAP, HR or cerebral perfusion pressure (CPP) whether initial ICP was normal or elevated.RésuméLes ejfets de l’atracurium sur la pression intracrânienne (ICP) ont été investigués sur six chats présentant une pression intracrénienne normale ou élevée. Les chats ont été anesthésié avec du pentobarbitone (33mg·kg-1) administré par voie péritoniale, l’acepromazine (0.6 mg·kg-1) et des doses additionnelles de fentanyl (p.r.n. ≅ 20 μg·kg-1), intubés et ventilés avec le protoxide d’azote dans l’oxygène. La pression artérielle moyenne (MAP) fréquence cardiaque (HR), réponse neuromusculaire, et la pression intracrânienne ont été enregistrés d’une façon continue. Après létablissement des effets de l’atracurium lors d’ une pression intracrânienne normale ainsi qu’après le rétablissement de la fonction neuromusculaire, les solutions de lactate Ringer’s à pH-ajusté a été injectés dans la grande citerne jusqu’ à l’obtention de la pression intracrânienne de base de 26 ± 2 mmHg. L’atracurium a été ensuite administré afin de déterminer son ejfet dans des conditions d’une pression intracrânienne élevée. L’abolition complète des contractions a été obtenu après 68 ± 15 sec avec 0.4mg·kg-1 d’atracurium. Aucun changement significatif n’a été observé dans la pression intracrânienne, la pression artérielle moyenne à fréquence cardiaque ou la pression de perfusion cérébrate (CPP) lorsque la pression intracrânienne était normale ou élevé.

Paraben preservatives do not increase intracranial pressure in cats

It has been hypothesized recently that succinylcholine-associated increases in intracranial pressure (ICP) are caused by the paraben preservatives contained in multidose vials. We tested that hypothesis in a standard feline model to determine the effects on ICP of equal-volume injections of preservative-free succinylcholine, succinylcholine with preservatives from multi-dose vials that contain both propylparaben and methylparaben, these preservatives alone at five times the dose contained in the succinylcholine, and normal saline. The preservatives alone increased ICP by 0.08 +/- 0.08 mmHg (+/- standard error; not significant). Normal saline had no effect on ICP. Preservative-free succinylcholine and succinylcholine with preservatives increased ICP by 4.2 +/- 0.10 and 3.8 +/- 0.07 mmHg respectively (P less than 0.01 compared to the preservatives alone and normal saline). The 99% upper confidence limit for the increase in ICP induced by the preservatives alone was 0.42 mmHg. This result suggests that parabens do not cause or substantially augment the ICP increase associated with succinylcholine administration.