Richard J. Sperry

Respiratory Effects of Clonidine Alone and Combined with Morphine, in Humans

Because only limited and controversial data exist concerning the respiratory effects of clonidine in humans, the authors evaluated the respiratory effects of clonidine alone and in combination with morphine, in 12 healthy adult males. Subjects received clonidine (0.3-0.4 mg orally), morphine (0.21 mg/kg intramuscularly), or the same doses of the two drugs combined, at three separate sessions in a randomized fashion. The study was balanced for all possible sequences of drug administration. Blood pressure, heart rate, hemoglobin oxygen saturation via finger pulse oximetry, and ventilatory and occlusion pressure responses to CO2 were obtained before and 20, 40, 60, 90, 120, 180, 240, 300, and 360 min after administration of drug or drug combination. Systolic blood pressure decreased significantly only in the clonidine and clonidine plus morphine groups (P less than 0.05). Hemoglobin oxygen saturation decreased by a statistically significant (P less than 0.05), though clinically minor, degree only in the morphine or morphine plus clonidine groups. Clonidine alone did not depress the slope of either the ventilatory or the occlusion pressure response to CO2. In addition, clonidine did not significantly worsen morphine-induced depression of the slope of the ventilatory and occlusion pressure responses in the drug combination group. Both the ventilatory and occlusion pressure responses to CO2 were shifted to the right in all three drug groups (P less than 0.05) but were shifted to a significantly lesser degree by clonidine alone than by morphine and morphine plus clonidine. In healthy young adult males, clonidine alone produces little respiratory depression and does not significantly potentiate morphine-induced respiratory depression.

Fentanyl and Sufentanil Increase Intracranial Pressure in Head Trauma Patients

Although opioids frequently are administered to patients with severe head trauma, the effects of such drugs on intracranial pressure are controversial. Nine patients with severe head trauma were studied for the effects of fentanyl and sufentanil on intracranial pressure (ICP). In all patients, ICP monitoring was instituted before the study. Full neuromuscular blockade was achieved with vecuronium bromide before the administration of either fentanyl (3 micrograms.kg-1) or sufentanil (0.6 microgram.kg-1) as an intravenous bolus over a 1-min period in a masked and random fashion. Patients received the other opioid in the same fashion 24 h later. Arterial blood pressure, heart rate, and ICP were recorded continuously for the 1 h after drug administration. Fentanyl was associated with an average ICP increase of 8 +/- 2 mmHg, and sufentanil with an increase of 6 +/- 1 mmHg. These increases were statistically significant. Both drugs produced clinically mild decreases in mean arterial blood pressure (fentanyl, 11 +/- 6 mmHg; sufentanil, 10 +/- 5 mmHg) that nevertheless were statistically significant. No significant changes in heart rate occurred. These results indicate that modest doses of potent opioids can significantly increase ICP in patients with severe head trauma.

Intracranial pressure, middle cerebral artery flow velocity, and plasma inorganic fluoride concentrations in neurosurgical patients receiving sevoflurane or isoflurane.

This study examined the concentration-related effects of sevoflurane and isoflurane on cerebral physiology and plasma inorganic fluoride concentrations. Middle cerebral artery flow velocity (Vmca), intracranial pressure (ICP), electroencephalogram (EEG) activity, and jugular bulb venous oxygen saturation were measured, and cerebral perfusion pressure (CPP) and estimated cerebral vascular resistance (CVRe) were calculated at baseline and at 0.5, 1.0, and 1.5 minimum alveolar anesthetic concentration (MAC) sevoflurane (n = 8) or isoflurane (n = 6). Mannitol 0.5-0.75 g/kg was given before dural incision, and blood was sampled for plasma inorganic fluoride during surgery and for up to 72 h postoperatively. Both sevoflurane and isoflurane decreased Vmca (to 31 +/- 12 - 36 +/- 14 cm/s, mean +/- SD), did not significantly alter ICP (13 +/- 9 - 15 +/- 11 mm Hg), and did not cause epileptiform EEG activity. With sevoflurane, decreased Vmca was accompanied by decreased CPP and unchanged CVR (e) at 0.5 MAC, and unchanged CPP and increased CVRe at 1.0 and 1.5 MAC. Plasma inorganic fluoride was 39.0 +/- 12.9 micro M at the end of anesthesia (3.2 +/- 2.0 MAC hours) with sevoflurane, similar to the value (36.2 +/- 3.9 micro M) for 3.7 +/- 0.1 MAC hours sevoflurane in patients not receiving mannitol. Decreased Vmca during sevoflurane presumably results from decreased cerebral metabolic rate, with CVRe changing secondarily in accord with CPP. Plasma inorganic fluoride does not seem to be altered by mannitol-induced diuresis. Implications: In neurosurgical patients, sevoflurane decreased middle cerebral artery flow velocity and caused no epileptiform electroencephalogram activity and no increase of intracranial pressure or plasma inorganic fluoride. These effects are suitable for neurosurgery. Two other possible effects of sevoflurane, i.e., increased cerebrospinal fluid volume and/or intracranial elastance, may not be suitable for neurosurgery and warrant further study. (Anesth Analg 1997;85:587-92)

Endotracheal Tube Cuff Pressure Increases Significantly During Anterior Cervical Fusion with the Caspar Instrumentation System

&NA; To determine whether endotracheal tube cuff pressure increases significantly with surgical retraction and cervical spine distraction during anterior cervical spine surgery with Caspar instrumentation, we prospectively studied 10 patients undergoing this procedure. The tracheas of all patients were intubated with a Mallinckrodt Hi‐Lo® endotracheal tube. Tracheal tube cuff pressures measured with a transducer system were 42.4 mm Hg ± 7.0 mm Hg (SEM) after intubation and cuff inflation. Air was removed from the endotracheal tube cuff until the trachea was just barely sealed at a cuff pressure of 15.2 mm Hg ± 1.6 mm Hg. The endotracheal tube cuff pressure was readjusted to “just‐seal” pressure before the surgeons introduced the Caspar instrumentation. The cuff pressure with traction and distraction was 43.2 mm Hg ± 5.0 mm Hg. This pressure was significantly increased from the “just‐seal” pressure, and from the cuff pressure after instrumentation was discontinued (9.8 mm Hg ± 2.3 mm Hg). We conclude that anterior cervical spine surgery with Caspar instrumentation is associated with a significant increase in endotracheal tube cuff pressure. (Anes Analg 1993;76:1318‐21)

Effects of hypoxemia on regional blood flows during anesthesia with halothane, enflurane, or isoflurane.

Hypoxemia during anesthesia can cause severe morbidity and mortality. To determine how the volatile anesthetics alter the normal hemodynamic compensation for hypoxemia, we investigated the effects of various anesthetics on regional blood flows during normoxemia and during normocapnic hypoxemia (FIO2 0.12 for 20 min) in rats. Using the radioactive microsphere method, organ blood flows were determined in animals anesthetized with 1 MAC of halothane, enflurane, or isoflurane and in awake animals. Brain blood flow increased significantly with hypoxemia in awake animals. However, brain blood flow decreased in all anesthetized animals that were hypoxemic. Coronary blood flow also increased significantly with hypoxemia in awake animals. In the presence of volatile anesthetics, coronary blood flow decreased, a decrease that was unchanged with hypoxemia. Thus, there was a large difference in brain and coronary blood flows between awake hypoxemic and anesthetized hypoxemic animals. Hypoxemia did not alter the magnitude of renal, gastrointestinal tract, or total hepatic blood flows in awake animals. However, all three blood flows decreased significantly in anesthetized hypoxemic animals. We conclude that volatile anesthetics modify the compensatory responses to hypoxemia that occur in awake animals, resulting in decreased blood flow to vital organs.