Linda S. Barter

Hemodynamic effects of dexmedetomidine in isoflurane-anesthetized cats

OBJECTIVE To characterize the hemodynamic effects of dexmedetomidine in isoflurane-anesthetized cats. STUDY DESIGN Prospective experimental study. ANIMALS Six healthy adult female cats weighing 4.6 ± 0.8 kg. METHODS Dexmedetomidine was administered intravenously using target-controlled infusions to maintain nine plasma concentrations between 0 and 20 ng mL(-1) in isoflurane-anesthetized cats. The isoflurane concentration was adjusted for each dexmedetomidine concentration to maintain the equivalent of 1.25 times the minimum alveolar concentration, based on a previous study. Heart rate, systemic and pulmonary arterial pressures, central venous pressure, pulmonary artery occlusion pressure, body temperature, and cardiac output were measured at each target plasma dexmedetomidine concentration. Additional variables were calculated. Arterial and mixed-venous blood samples were collected for blood gas, pH, and (on arterial blood only) electrolyte, glucose and lactate analysis. Plasma dexmedetomidine concentration was determined for each target. Pharmacodynamic models were fitted to the data. RESULTS Heart rate, arterial pH, arterial bicarbonate concentration, mixed-venous PO(2) , mixed-venous pH, mixed-venous hemoglobin oxygen saturation, cardiac index, stroke index, and venous admixture decreased following dexmedetomidine administration. Arterial blood pressure, central venous pressure, pulmonary arterial pressure, pulmonary arterial occlusion pressure, packed cell volume, PaO(2) , PaCO(2) , arterial hemoglobin concentration, mixed-venous PCO(2) , mixed-venous hemoglobin concentration, ionized calcium concentration, glucose concentration, rate-pressure product, systemic and pulmonary vascular resistance indices, left ventricular stroke work index, arterial oxygen concentration, and oxygen extraction increased following dexmedetomidine administration. Most variables changed in a dexmedetomidine concentration-dependent manner. CONCLUSION AND CLINICAL RELEVANCE The use of dexmedetomidine as an anesthetic adjunct is expected to produce greater negative hemodynamic effects than a higher, equipotent concentration of isoflurane alone.

The differential effects of halothane and isoflurane on electroencephalographic responses to electrical microstimulation of the reticular formation

Isoflurane and halothane cause electroencephalographic (EEG) depression and neuronal depression in the reticular formation, a site critical to consciousness. We hypothesized that isoflurane, more than halothane, would depress EEG activation elicited by electrical microstimulation of the reticular formation. Rats were anesthetized with either halothane or isoflurane and stimulating electrodes were positioned in the reticular formation. In a crossover design, anesthetic concentration was adjusted to 0.8 and 1.2 minimum alveolar concentration (MAC) of halothane or isoflurane and electrical microstimulation was performed and the EEG responses were recorded. Microstimulation increased the spectral edge and median edge frequencies 2–2.5 Hz at 0.8 MAC for halothane and isoflurane and 1.2 MAC halothane. At 1.2 MAC isoflurane, burst suppression occurred and microstimulation decreased the period of isoelectricity (24% ± 19% to 8% ± 7%; P < 0.05), whereas the spectral edge and median edge frequencies were unchanged. At anesthetic concentrations required to produce immobility, the cortex remains responsive to electrical microstimulation of the reticular formation, although the EEG response is depressed in the transition from 0.8 to 1.2 MAC. These data indicate that cortical neurons remain responsive to synaptic input during isoflurane and halothane anesthesia.

Propofol's effects on nociceptive behavior and spinal c-fos expression after intraplantar formalin injection in mice with a mutation in the gamma-aminobutyric acid-type(A) receptor beta3 subunit.

We investigated whether propofol affected nociceptive behavior and fos-like immunoreactivity (FLI) in the lumbo-sacral spinal cord after intraplantar formalin injection in wild-type (WT) mice and in mutant mice harboring a point mutation of the gamma-aminobutyric acid type A receptor, which renders them resistant to propofol. Bolus injection of propofol (30 mg/kg IV) in WT mice reduced phase 1 formalin-evoked behavior over the initial 2–3 min but did not alter phase 2 behavior or spinal FLI (64 ± 19 cells/section) compared with WT mice receiving intralipid vehicle plus intraplantar formalin (57 ± 19 cells/section). Most FLI was restricted to superficial dorsal horn laminae ipsilateral to the formalin injection. WT mice receiving a 60-min propofol infusion were anesthetized throughout and did not display nociceptive behavior but had FLI (58 ± 11 cells/section) that did not differ significantly from the other WT groups. Mutant mice receiving bolus injection of propofol (30 mg/kg) and intraplantar formalin were not anesthetized and exhibited nociceptive behavior. The total FLI in the spinal cord was 47 ± 29 cells/section. These data indicate that although propofol produces anesthesia, it does not prevent the FLI that is associated with nociception, a finding consistent with propofol lacking analgesic properties.

Immobilizing Doses of Halothane, Isoflurane or Propofol, Do Not Preferentially Depress Noxious Heat-Evoked Responses of Rat Lumbar Dorsal Horn Neurons with Ascending Projections

BACKGROUND: The spinal cord is an important site where volatile anesthetics decrease sensation and produce immobility. Beyond this knowledge, our understanding of a site of anesthetic action is limited. Previous evidence suggests that dorsal horn neurons with ascending projections may be more susceptible to depression by general anesthetics than local spinal interneurons. In this study we evaluated the effects of volatile and injectable general anesthetics on lumbar dorsal horn neurons with and without ascending projections. METHODS: Thirty-seven adult male rats underwent laminectomies at C1, for placement of a stimulating electrode, and T13/L1, for extracellular recording from the spinal cord dorsal horn. Neuronal responses to heat were evaluated under two doses of halothane, isoflurane, or propofol anesthesia. RESULTS: Under both halothane and isoflurane anesthesia, increasing the dose from 0.8 to 1.2 minimum alveolar concentration (MAC) had no significant effect on heat-evoked responses in neurons that had ascending projections identified via antidromic stimulation (AD) or those without ascending projections (nAD). Heat responses in AD neurons 1 min after IV administration of 3 and 5 mg/kg of propofol were reduced to 60% ± 18% (mean ± se) and 39% ± 14% of control respectively. Similarly, in nAD neurons responses were reduced to 56% ± 14% and 50% ± 10% of control by 3 and 5 mg/kg propofol respectively. CONCLUSIONS: Our findings suggest, at peri-MAC concentrations, these general anesthetics do not preferentially depress lumbar dorsal horn neurons with ascending projections compared to those with no identifiable ascending projections.

Thymoma removal in a cat with acquired myasthenia gravis: a case report and literature review of anesthetic techniques

UNLABELLED HISTORY AND PRESENTATION: A 12 year old, 4.2 kg, domestic long hair, castrated male cat was presented with regurgitation, inability to retract the claws, general weakness, cervical ventroflexion and weight loss. A thymic mass was evident on radiographs. Acetylcholine receptor antibody titer was positive for acquired myasthenia gravis (MG). Thymectomy via midline sternotomy was scheduled. ANESTHETIC MANAGEMENT:  Oxymorphone and atropine were administered subcutaneously as premedication, and anesthesia was induced with etomidate and diazepam given intravenously to effect. The cats trachea was intubated and anesthesia was maintained with isoflurane in oxygen, and continuous infusions of remifentanil and ketamine. Epidural analgesia with preservative-free morphine was administered prior to surgery. Postoperative analgesia was provided by oxymorphone subcutaneously, interpleural bupivacaine, and fentanyl infusion. Postoperative complications included airway obstruction, hypoxemia and hypercapnia. FOLLOW-UP The cat was discharged 3 days after surgery. Discharge medications included pyridostigmine and prednisone. Nine days after surgery, the cat had a significant increase in its activity level, and medications were discontinued. Histopathologically, the mass was consistent with a thymoma. Approximately 6 weeks later the cat became weak again and pyridostigmine and prednisone administration was resumed. CONCLUSION The perioperative management of patients with MG for transsternal thymectomy is a complex task. The increased potential for respiratory compromise requires the anesthesiologist to be familiar with the underlying disease state, and the interaction of anesthetic and non-anesthetic drugs with MG. Careful monitoring of ventilation and oxygenation is indicated postoperatively.

Hexafluorobenzene acts in the spinal cord, whereas o-difluorobenzene acts in both brain and spinal cord, to produce immobility.

BACKGROUND:Previous work demonstrated that isoflurane and halothane act on the spinal cord rather than on the brain to produce immobility in the face of noxious stimulation. These anesthetics share many effects on specific receptors, and thus do not test the broad applicability of the mediation of immobility by the cord. We sought to test such an applicability by determining whether the cord mediated the immobilizing effects of two aromatic anesthetics that differ greatly in their ability to block N-methyl-d-aspartate receptors. METHODS:We investigated the actions of hexafluorobenzene (HFB) and o-difluorobenzene (ODFB) using an intact goat model that allowed selective delivery of anesthetics to the brain. Because our results suggested a significant cerebral effect of ODFB, in other goats we administered halothane 0.5% to the brain, while determining the ODFB concentration delivered to the body (the cord) required for immobility. We chose halothane because the present and previous studies found that cerebral halothane concentrations alone required for producing immobility far exceeded those required in the cord. We also applied the above techniques to another benzene-containing anesthetic, propofol. RESULTS:Prebypass minimum alveolar concentration (MAC) for HFB was 0.82% ± 0.14% (mean ± sd); increased to 2.04% ± 0.8% (P < 0.01) during selective delivery to the cranial circulation; and returned to 0.79% ± 0.28% postbypass. Corresponding values for ODFB were 0.46% ± 0.07%, 0.63% ± 0.12% (P < 0.05), and 0.44% ± 0.10%. ODFB MAC was 0.32% ± 0.17% during selective halothane delivery to brain. But when ODFB was administered to the whole body, MAC was 0.37% ± 0.05%, (NS). Like HFB, the halothane requirement increased threefold when delivered only to the head. In four of five animals, propofol requirements increased by 240%, but in one animal propofol requirements decreased, and the overall change was not statistically significant. CONCLUSIONS:These data suggest that HFB, like halothane, produces immobility, predominantly by a spinal cord action, and that HFB differs from ODFB with respect to brain versus spinal sites of action. Nonetheless, although ODFB can produce immobility via a cerebral action, it also can do this via an independent action in the spinal cord. Thus, our results continue to support the spinal cord as the primary site at which inhaled anesthetics, and perhaps propofol, produce immobility.

The effect of isoflurane and halothane on electroencephalographic activation elicited by repetitive noxious c-fiber stimulation.

Windup is the progressive increase in neuronal response to a repetitive noxious stimulus. This response is most often observed in the spinal cord, but it is unclear how this response is manifested in supraspinal structures. We investigated the effects of isoflurane and halothane on electroencephalographic responses to repetitive noxious electrical stimuli (20 pulses at 0.1, 1 and 3 Hz) applied to the tail in rats. Halothane and isoflurane concentrations were adjusted to 0.8 and 1.2 minimum alveolar concentration (MAC), where MAC is the concentration needed to prevent gross and purposeful movement in 50% of animals. At 0.8 MAC halothane, the 3 Hz stimulus caused electroencephalographic (EEG) activation primarily by increasing the median edge frequency (MEF), while at 1.2 MAC halothane the spectral edge frequency (SEF) was increased by the 1 and 3 Hz stimuli, and the MEF was increased by the 3 Hz stimuli. At 0.8 MAC isoflurane, the 1 and 3 Hz stimuli evoked EEG activation by increasing the MEF and SEF, while at 1.2 MAC only the MEF was increased by the 1 Hz stimulus. No EEG activation occurred with the 0.1 Hz repetitive stimulus with either isoflurane or halothane. These data suggest that repetitive electrical stimulation normally associated with windup in spinal neurons can evoke EEG activation.

Cardiovascular and respiratory effects of incremental doses of dopamine and phenylephrine in the management of isoflurane-induced hypotension in cats with hypertrophic cardiomyopathy

OBJECTIVE To determine cardiopulmonary effects of incremental doses of dopamine and phenylephrine during isoflurane-induced hypotension in cats with hypertrophic cardiomyopathy (HCM). ANIMALS 6 adult cats with severe naturally occurring HCM. PROCEDURES Each cat was anesthetized twice (once for dopamine treatment and once for phenylephrine treatment; treatment order was randomized). Hypotension was induced by increasing isoflurane concentration. Cardiopulmonary data, including measurement of plasma concentration of cardiac troponin I (cTnI), were obtained before anesthesia, 20 minutes after onset of hypotension, and 20 minutes after each incremental infusion of dopamine (2.5, 5, and 10 μg/kg/min) or phenylephrine (0.25, 0.5, and 1 μg/kg/min). RESULTS Mean ± SD end-tidal isoflurane concentration for dopamine and phenylephrine was 2.44 ± 0.05% and 2.48 ± 0.04%, respectively. Cardiac index and tissue oxygen delivery were significantly increased after administration of dopamine, compared with results after administration of phenylephrine. Systemic vascular resistance index was significantly increased after administration of phenylephrine, compared with results after administration of dopamine. Oxygen consumption remained unchanged for both treatments. Systemic and pulmonary arterial blood pressures were increased after administration of both dopamine and phenylephrine. Acid-base status and blood lactate concentration did not change and were not different between treatments. The cTnI concentration increased during anesthesia and infusion of dopamine and phenylephrine but did not differ significantly between treatments. CONCLUSIONS AND CLINICAL RELEVANCE Dopamine and phenylephrine induced dose-dependent increases in systemic and pulmonary blood pressure, but only dopamine resulted in increased cardiac output. Hypotension and infusions of dopamine and phenylephrine caused significant increases in cTnI concentrations.

Effects of acetylcholinesterase inhibition on quality of recovery from isoflurane-induced anesthesia in horses

OBJECTIVE To compare effects of 2 acetylcholinesterase inhibitors on recovery quality of horses anesthetized with isoflurane. ANIMALS 6 horses in phase 1, 7 horses in phase 2A, and 14 horses in phase 2B. PROCEDURES The study comprised 3 phases (2 randomized, blinded crossover phases in horses undergoing orthopedic procedures and 1 prospective dose-determining phase). In phase 1, horses were anesthetized with isoflurane and received neostigmine or saline (0.9% NaCl) solution prior to anesthetic recovery. Phase 2A was a physostigmine dose-determining phase. In phase 2B, horses were anesthetized with isoflurane and received neostigmine or physostigmine prior to recovery. Objective recovery events were recorded and subjective visual analogue scale scores of recovery quality were assigned from video recordings. RESULTS Recovery measures in phase 1 were not different between horses receiving neostigmine or saline solution. In phase 2A, 0.04 mg of physostigmine/kg was the highest cumulative dose that did not cause clinically relevant adverse behavioral or gastrointestinal effects. Horses receiving physostigmine had higher mean ± SD visual analogue scale recovery scores (70.8 ± 13.3 mm) than did horses receiving neostigmine (62.4 ± 12.8 mm) in phase 2B, with fewer attempts until sternal and standing recovery. Incidence of colic behavior did not differ among groups. CONCLUSIONS AND CLINICAL RELEVANCE Inhibition with physostigmine improved anesthetic recovery quality in horses anesthetized with isoflurane, compared with recovery quality for horses receiving neostigmine. Inhibition of central muscarinic receptors by inhalation anesthetics may underlie emergence delirium in horses recovering from anesthesia.

Rat dorsal horn nociceptive-specific neurons are more sensitive than wide dynamic range neurons to depression by immobilizing doses of volatile anesthetics: an effect partially reversed by the opioid receptor antagonist naloxone.

BACKGROUND: The mechanism and site of action within the spinal cord by which volatile anesthetics produce immobility are not well understood. Little work has been done directly comparing anesthetic effects on neurons with specific functional characteristics that mediate transfer of nociceptive information within the spinal cord. METHODS: Adult male rats were anesthetized and prepared for extracellular single-unit recordings from the lumbar dorsal horn. Nociceptive-specific (NS) and wide dynamic range (WDR) neurons were identified and noxious heat-evoked neuronal spike rates evaluated at 0.8 and 1.2 anesthetic minimum alveolar anesthetic concentration (MAC) halothane or isoflurane. In another group, noxious heat-evoked responses from NS neurons were evaluated at 0.8, 1.2 MAC halothane, and 1.2 MAC halothane plus IV naloxone (0.1 mg/kg). RESULTS: Increasing halothane from 0.8 to 1.2 MAC reduced the heat-evoked neuronal responses of NS neurons (n = 9) from 827 ± 122 (mean ± se) to 343 ± 48 spikes/min (P < 0.05) but not WDR neurons (n = 9), 617 ± 79 to 547 ± 78 spikes/min. Increasing isoflurane from 0.8 to 1.2 MAC reduced the heat-evoked neuronal response of NS neurons (n = 9) from 890 ± 339 to 188 ± 97 spikes/min (P < 0.05) but did not alter the response of WDR neurons (n = 9) in which evoked spike rate went from 576 ± 132 to 601 ± 119 spikes/min. In a separate group, the response of NS neurons went from 282 ± 60 to 74 ± 32 spikes/min (P < 0.05) when halothane was increased from 0.8 to 1.2 MAC. IV administration of naloxone increased the heat-evoked response to 155 ± 46 spikes/min (P < 0.05). CONCLUSIONS: NS but not WDR neurons in the lumbar dorsal horn are depressed by peri-MAC increases of halothane and isoflurane. This depression, at least with halothane, can be partially reversed by the opioid antagonist naloxone. Given that opioid receptors are not likely involved in the mechanisms by which volatile anesthetics produce immobility, this suggests that, although the neuronal depression is of substantial magnitude and occurs concurrent to the production of immobility, it may not play a major role in the production of this anesthetic end point.