Effects of Midazolam on Cerebral Hemodynamics and Cerebral Vasomotor Responsiveness to Carbon Dioxide

Abstract

Although it is known that hypercarbia increases and benzodiazepines decrease cerebral blood flow (CBF), the effects of benzodiazepines on CBF responsiveness to CO2 are not well documented. The influence on CBF and CBF-C02 sensitivity of placebo or midazolam, which is a new water-soluble benzodiazepine, was measured in eight healthy volunteers using the noninvasive 133Xe inhalation method for CBF determination. Under normocarbia, midazolam decreased CBF from 40.6 ± 3.2 to 27.0 ± 5.0 ml 100 g−1 min−1 (x̄ ± SD). At a later session under hypercarbia, CBF was 58.8 ± 4.4 ml 100 g−1 min−1 after administration of placebo, and 49.1 ± 10.2 ml 100 g−1 min−1 after midazolam. The mean of the slopes correlating Paco2 and CBF was significantly steeper with midazolam (2.5 ± 1.2 ml 100 g−1 min−1 mm Hg−1) than with placebo (1.5 ± 0.4 ml 100 g−1 min−1 mm Hg−1). Our results suggest that midazolam may be a safe agent to use in patients with intracranial hypertension, since it decreases CBF and thus cerebral blood volume; however, it should be administered with caution in nonventilated patients with increased intracranial pressure, since its beneficial effects on cerebrovascular tone can be readily counteracted by the increase in arterial CO2 tension induced by this drug.

Cerebral Autoregulation is Influenced by Carbon Dioxide Levels in Patients with Septic Shock

“…There was no correlation between PaCO 2 and the initial VMCA. Fourteen patients (66%) had impaired cerebral autoregulation, including seven of the 14 patients (50%) with a PaCO 2 < 40 mmHg [28][29][30][31][32][33][34][35][36][37] and all seven of the patients with a PaCO 2 > 40 mmHg [41][42][43][44][45][46][47][48][49] (P = 0.046). Specifically, 4/9 (44%) patients with PaCO 2 < 35 mmHg, 7/9 (77%) with PaCO 2 between 35 and 42 mmHg, and 3/3 (100%) with PaCO 2 > 42 mmHg had impaired autoregulation.…”

“…Steady state conditions were maintained during the study, and we avoided hyperglycemia, extreme acidosis, and uremia, and changes in temperature and hemoglobin concentration, all factors that are known to affect cerebral autoregulation [18]. The drugs used for sedation or analgesia and norepinephrine do not influence cerebral autoregulation [32][33][34], so that one can assume that modifications in VMCA were due only to changes in MAP.…”

Changing practices in neuroanaesthesia

“…La r6ponse au CO2 6tait maintenue. 73 L'importance des r6ductions de d6bit et de m6tabolisme c6r6bral produit par les benzodiaz6pines est probablement de niveau interm6diaire entre celles produites par les narcotiques (minimal) et les barbituriques (substantiel). En utilisant son mod61e de riot veineux chez le chien, Michenfeider a observ6 une consommation minimale d'oxyg~ne c6r6brale de l'ordre de 2,2 ml.…”

“…CO2 responsiveness was preserved. 73 The extent of the CBF-CMR reduction produced by benzodiazepines is probably intermediate between the decreases caused by narcotics (minimal) and barbiturates (substantial). Using the canine venous outflow model, Michenfelder observed a minimum CMRO2 of 2.2 ml.…”

Effects of topical and intravenous JM-1232(−) infusion on cerebrovascular reactivity in rats

“…Furthermore, under background anesthesia of isoflurane, JM-1232(−) did not affect the pial arteriolar dilative response to hypercapnia. Both midazolam [10,11] and propofol [11,12] were shown to maintain cerebral CO 2 response. With regard to its response to hypercapnia, In the present study, basal anesthesia by isoflurane was needed for stable experiment.…”