Michael F. Heine

Hypoxia, excitotoxicity, and neuroprotection in the hippocampal slice preparation

The excitotoxic hypothesis postulates a central role for the excitatory amino acids (EAAs) and their receptors in the neuronal damage that ensues cerebral ischemia-hypoxia and numerous other brain disorders. A major premise of the excitotoxic hypothesis is that neuronal protection can be achieved via blockade of EAA receptors with specific antagonists. This paper describes the use of the rat hippocampal slice preparation in the evaluation of various EAAs and their analogues for their potency as excitotoxins (agonists) and antagonists of the NMDA and the kainate/AMPA glutamate receptor subtypes. The hypersensitivity of hypoxic hippocampal slices to the presence of excitotoxins provided us with an inexpensive, sensitive tool to distinguish between structurally similar compounds. Moreover, these studies indicate that hypoxic neuronal damage cannot solely result from an excitotoxic mechanism; the involvement of voltage-dependent calcium channels in such damage is likely, as is evident from experiments performed in calcium-depleted medium and with the non-competitive NMDA antagonist MK-801. At sub-toxic doses, quinolinate, a tryptophan metabolite implicated in Huntingtons disease, appears to be a strong potentiator of the toxicity of all excitotoxins tested.

Side effects during continuous epidural infusion of morphine and fentanyl

Respiratory effects, nausea, somnolence, and pruritus were compared during a 48-hr period of continuous epidural morphine (n = 34) and fentanyl (n = 32) infusion in 66 patients following elective total replacement of the hip or knee joint. Respiratory effects were assessed by PaCO2. Side effects were assessed by visual analogue scale and considered to be present when the score was above 30. Assessment was made at preoperative visits then 3, 6, 12, 24, 36, and 48 hr after the epidural injection. The bolus dose and subsequent infusion rate were 3,900 ± 1,300 μg and 427 ± 213 μg · hr−1 for morphine, and 85 ± 46 μg and 56 ± 27 μg · hr−1 for fentanyl. Pain relief was similar in both groups. In the morphine group, PaCO2 elevation and nausea occurred over a period of more than 12 hr (P < 0.05). In the fentanyl group, there was no PaCO2 change, and nausea was confined to the first few hours. Nausea was more severe (P < 0.01 at six hours and more frequent (24 hr cumulative incidence, 53 vs 28%, P < 0.05) in the morphine group. Somnolence was prominent within several hours in two-thirds of patients in both groups. Somnolence continued to decline thereafter in the morphine group, but it was demonstrable in approximately half of the patients throughout the second day in the fentanyl group. The incidence was higher in the fentanyl group at the 48th hr (P < 0.05). There was a quadratic increase in pruritus over time (P < 0.001), and it was more severe in the morphine group (P < 0.001). Pruritus was generalized in the morphine group; but it was segmental in the fentanyl group. It remained the side effect of most clinical concern during the second day in both groups. The temporal course of respiratory effect and nausea were similar to that which follows a bolus epidural injection. Side effects were less during the second day of infusion in both groups with the notable exception of pruritus. Side effects were generally less in the fentanyl group. The continuous epidural infusion of opioids, after the initial bolus-related side effects, appears to be a safe technique for prolonged and steady pain relief with minimal side effects.RésuméSoixante-six patients subissant un remplacement total de hanche ou de genou participent à cette étude. Les effets respiratoires, les nausées, la somnolence et le prurit associées à une perfusion épidurale continue de morphine (n = 34) ou de fentanyl (n — 32) sont évalués durant les 48 heures qui suivent la chirurgie. Les effets respiratoires sont évalués par la mesure de la PaCO2. Une échelle analogue visuelle sert à évaluer la sévérité des nausées, le niveau de somnolence et l’intensité du prurit. Un pointage supérieur à 30 est nécessaire pour marquer la présence de ces symptômes. L’évaluation est faite lors de la visite préopératoire, puis 3, 6, 12, 24, 36, et 48 heures après l’injection épidurale. La dose initiale et la vitesse de perfusion sont 3 900 ± 1 300 μg et 427 ± 213 μg · h−1 pour la morphine, et 85 ± 46 μg et 56 ± 27 μg · h−1 pour le fentanyl. L’analgésie postopératoire est comparable entre les deux groupes de traitement. Dans le groupe morphine, les nausées et les élévations de la PaCO2 surviennent pendant plus de 12 h après l’injection initiale, alors que dans le groupe fentanyl, ces effets ne sont présents que dans les premières heures de perfusion épidurale (P < 0,05). Dans le groupe morphine, les nausées sont plus sévères au cours des premières six heures (P < 0,01) et plus fréquentes (incidence de 53% versus 28% sur une période de 24 heures, P < 0,05) que dans le groupe fentanyl. Les deux tiers des patients de chaque groupe présentent une somnolence importante plusieurs heures après le début du traitment. Le degré de somnolence diminue rapidement par la suite chez les patients du groupe morphine, alors que près de la moitié des patients du groupe fentanyl sont encore somnolents au deuxième jour de traitement. L’incidence de somnolence à 48 heures demeure plus élevées dans le groupe fentanyl (P < 0,05). Le prurit est plus sévère dans le groupe morphine (P < 0,001) et augmente de façon quadratique dans le temps chez les patients de deux groupes (P < 0,001). Dans le groupe morphine, le prurit est généralisé alors qu ’il est plutôt segmentaire dans le groupe fentanyl. Le prurit représente l’effet secondaire le plus important au deuxieme jour dans les deux groupes. L’évolution des effets respiratoires et des nausees dans le temps est semblable a celle retrouvee aprés l’injection unique de ces narcotiques dans l’espace epidural. Les effets secondaires, a l’exception du prurit, sont moindres au deuxiéme jour dans les deux groupes, mais de facon générale, Us sont moins importants dans le groupe fentanyl. La perfusion épidurale continue de morphine ou de fentanyl est done une technique sécuritaire d’analgésie prolongee et elle est associee a peu d’effets secondaires autres que ceux causés par l’injection initiale (bolus) de ces narcotiques dans l’espace épidural.

Ventilator-associated pneumonia in critically ill stroke patients: Frequency, risk factors, and outcomes ☆,☆☆

PURPOSE Our main objective was to assess incidence, risk factors, and outcomes of ventilator-associated pneumonia (VAP) in stroke patients. MATERIALS AND METHODS After obtaining approval from the Human Studies Committee, we reviewed the electronic records from our intensive care unit database of 111 stroke patients on mechanical ventilation for more than 48 hours. Thirty-six risk factors related to disease and general health status, and 8 related to care-all assigned a priori-were collected and analyzed. Selected factors with univariate statistical significance (P < .05) were then analyzed with multivariate logistic regression. RESULTS Thirty-one patients developed pneumonia (28%). Methicillin-resistant Staphylococcus aureus (n = 12) and methicillin-sensitive S aureus (n = 7) were the most common pathogenic bacteria. Chronic lung disease, neurological status at admission as assessed by the National Institutes of Health Stroke Scale, and hemorrhagic transformation were the independent risk factors contributing to VAP. Worsening oxygenation index (arterial partial pressure of oxygen/fraction of inspired oxygen) and proton pump inhibitor use for ulcer prophylaxis were other potentially important factors. CONCLUSIONS Pneumonia appears as a frequent problem in mechanically ventilated stroke patients. Chronic lung disease history, severity of stroke level at admission, and hemorrhagic transformation of stroke set the stage for developing VAP. The duration of both mechanical ventilation and intensive care unit stay gets significantly prolonged by VAP, but it does not affect mortality.

The neurotoxicity of sulfur-containing amino acids in energy-deprived rat hippocampal slices

The rat hippocampal slice preparation and its electrophysiology were used to assess the toxicity of two sulfur-containing amino acids, L-cysteate (CA) and L-cysteine (CYS). Both compounds were innocuous under normal conditions but became toxic in energy-deprived (lack of oxygen or glucose) slices. CA and CYS toxicity was apparent as both reduced the number of slices that normally recover their neuronal function (evoked CA1 population spike) after a standardized period of hypoxia or glucose deprivation (GD). The competitive N-methyl-D-aspartate (NMDA) antagonist DL-2-amino-5-phosphonovalerate blocked the toxicity of both CA and CYS in hypoxic slices, but it was effective only against CYS toxicity in glucose-deprived slices. The glycine antagonist 7-chlorokynurenate blocked CA and CYS toxicity in hypoxic slices but was unable to block their toxicity in glucose-deprived tissue. Perfusing slices with medium containing a high magnesium concentration blocked the toxicity of CA in both hypoxic and glucose-deprived slices, a treatment that was ineffective against CYS toxicity under either condition. Calcium depletion from the perfusion medium completely blocked the damaging effect of both amino acids in hypoxic slices, but it only partially blocked the toxicity of CA and did not block that of CYS in glucose-deprived slices. These results suggest that CA and CYS activate different NMDA receptor subsets and other glutamate receptor subtypes. Moreover, the results indicate a possible difference between the mechanism that lead to hypoxic neuronal damage and the one that lead to hypoglycemic neuronal damage.

Cardiac sympathetic tone in anaesthetized diabetics

To assess cardiac sympathetic nervous function in diabetics, the heart rates attained following a pharmacological dose of intravenous atropine, 23 μg · kg−1, were studied under N2O, isoflurane anaesthesia in diabetics (n = 21) and nondiabetics (n = 30). Atropine-induced heart rate in diabetics was significantly lower than that in nondiabetics (95 ± 14 (SD) bpm vs 109 ±12 bpm, P < 0.001) and were closely related to preoperative orthostatic diastolic blood pressure change (r = 0.60, P < 0.01). There was some correlation between the atropine-induced heart rate and preoperative RR-variation in diabetics (r = 0.50, P < 0.05). The findings suggest that cardiac sympathetic function may also be impaired in diabetics with orthostatic hypotension.RésuméAfin d’évaluer la fonction du système nerveux sympathique cardiaque chez les diabétiques, la fréquence cardiaque obtenue après une dose pharmacologique intraveineuse d’atropine, 23 μg · kg−1, a été étudiée sous une anesthésie avec le protoxyde d’azote/oxygène/isoflurane chez des diabétiques (n = 21) et des non-diabétiques (n = 30). La fréquence cardiaque induite par l’atropine a été significativement plus basse que celle obtenue chez les non-diabétiques (95 ± 14 (SD) bpm vs 109 ± 12 bpm, P < 0,001) et ceci était étroitement corrélé avec les changements de la pression artérielle diastolique en période préopératoire et en position osthostatique (r = 0,60, P < 0.01). Il y avait une certaine corrélation entre la fréquence cardiaque induite par l’atropine et les variations RR en période préopératoire chez les diabétiques (r = 0,50, P < 0.05). Ceci suggère que la fonction sympathique cardiaque peut aussi être altérée chez les diabétiques présentant de l’hypotension orthostatique.

Mood during Epidural Patient-controlled Analgesia with Morphine or Fentanyl

Background Mood states during epidural opioids are not known. The authors studied the change in mood during the 48‐h period of epidural morphine and epidural fentanyl in 47 patients after elective hip or knee joint arthroplasty. Methods An epidural catheter was inserted at the L2‐L3 or L3‐L4 interspace. Anesthesia was induced with thiopenthal and maintained with isoflurane and nitrous oxide. One hour before the conclusion of the operation, patients received an epidural bolus injection of 2 mg morphine (n = 23) or 100 micro gram fentanyl (n = 24), followed by the same opiate (125 micro gram/ml morphine or 25 micro gram/ml fentanyl) epidurally delivered by a patient‐controlled analgesia (PCA) pump in the postoperative period for 48 h. Mood was assessed using the bipolar form of the Profile of Mood States before operation and 24 h, 48 h, and 72 h after operation. Results There was no significant difference in pain intensity between the groups during epidural PCA. Mood states became more positive over time in the patients who received morphine (P < 0.01 at 48 h) and negative in those who were given fentanyl (P < 0.01 at 24 and 48 h, respectively) compared with those before the operation, and they were more positive in the morphine than in the fentanyl group at 24 h, 48 h (P < 0.05), and 72 h (P < 0.01). Patients in the morphine group were more composed, agreeable, elated, confident, energetic, and clearheaded than were those in the fentanyl group (P < 0.05). There was no correlation between mood scores and pain scores in either group. There was an inverse correlation at 48 h between mood scores and plasma fentanyl concentrations (r = ‐0.58, P < 0.05). Conclusion Mood states are significantly more positive during epidural morphine PCA than they are during epidural fentanyl PCA.

The Effect of Intravenous Ranitidine and Metoclopramide on Behavior, Cognitive Function, and Affect

Both ranitidine and metoclopramide produce neuropsychiatric side effects. Concomitant use of these drugs preoperatively may produce adverse behavioral and emotional changes. Therefore, in 123 unpremedicated patients undergoing tubal occlusion, behavior, cognitive function, and affect were studied before and after a 2‐min intravenous injection of placebo (n = 30), ranitidine 50 mg (n = 32), metoclopramide 10 mg (n = 30), or both ranitidine 50 mg and metoclopramide 10 mg (n = 31). Cognitive function was evaluated by the responses to 11 statements devised to assess attitude toward anesthesia and surgery. Affect was assessed by the word chosen out of 11 word‐pairs as best describing the feelings at the time. After ranitidine injection, one patient seemed restless and five seemed drowsy. The changes were associated with subjective feelings of agitation (P < 0.05) and restlessness (P < 0.05). After metoclopramide injection, 6 (20%) developed akathisia, 13 (43.3%) seemed restless, and 8 (26.7%) seemed drowsy. The changes were associated with subjective sensation of jumpiness (P < 0.01) and discomfort (P < 0.05). When both ranitidine and metoclopramide were injected, 10 (32.3%) developed akathisia, 4 (12.4%) seemed restless, and 11 (35.5%) seemed drowsy. The changes were associated with subjective feelings of agitation (P < 0.05), jumpiness (P < 0.05), restlessness (P < 0.01), and upset (P < 0.05). Akathisia, a side effect of metoclopramide, seemed to be more prominent when ranitidine was added.

Butorphanol for the relief of shivering associated with extradural anesthesia in parturients

STUDY OBJECTIVE To assess the efficacy of butorphanol for the relief of shivering following the epidural administration of 2% lidocaine. DESIGN Randomized, double-blind study. SETTING Labor and delivery department of a university-affiliated hospital inpatient facility. PATIENTS Sixty-one healthy labor patients. INTERVENTIONS Patients who had sustained shivering associated with lidocaine epidural anesthesia were given normal saline or butorphanol 1 mg. Patients were observed for 20 minutes following the administration of a study solution. MEASUREMENTS AND MAIN RESULTS Shivering ceased within a mean time of 12.9 +/- 3.8 minutes in approximately 81% of the patients who received epidural butorphanol (p < 0.01), while 3% of the patients in the placebo group had no shivering following the administration of epidural saline. No sedation or changes in fetal heart rate were associated with epidural butorphanol. CONCLUSIONS Epidural butorphanol is effective in the treatment of postepidural shivering associated with epidural lidocaine. Epidural agonist opioids have been reported to be efficacious in the management of postepidural shivering. This study demonstrated that a partial agonist opioid also is effective in the treatment of postepidural shivering.

Phrenic nerve injury following scalenectomy in a patient with thoracic outlet obstruction

We present a case in which a patient with normal pulmonary reserve experienced orthopnea and hypoxia secondary to unilateral diaphragmatic paralysis following right scalenectomy. This operation was performed in an attempt to relieve neurovascular compromise at the thoracic outlet. To our knowledge, this association has not been previously described in the literature.

Can transnasal flexible fiberoptic laryngoscopy contribute to airway management decisions

Nasal endoscopic airway assessment is part of a common practice for otolaryngologists, especially those who are involved with head and neck oncology cases. Transnasal flexible fiberoptic laryngoscopy is a type of procedure that can be performed easily in an office environment under the combination of a topical anesthetic and a decongestant without resulting in any major patient discomfort (Fig. 1). Sawashima and Hirose developed today’s understanding of transnasal flexible fiberoptic endoscopy. Although it is named a laryngoscope, it actually provides excellent visual examination access to the nose, pharynx, posterior pharynx, epiglottis, and larynx, essentially all of the upper airway to the glottis. Pharyngeal and laryngeal functioning can be visualized easily in spontaneously breathing patients without much patient discomfort. Because it provides excellent access to the airway area of interest, transnasal flexible fiberoptic endoscopy has gained widespread acceptance among many types of medical specialists including otolaryngologists, emergency physicians, and speech-language pathologists. Currently, speech pathology specialists assess the swallowing process using a transnasal flexible fiberoptic laryngoscope. This procedure is called flexible endoscopic evaluation of swallowing, and it is the “gold standard” for the functional assessment of swallowing. Despite its well-established role in assessing the airway and swallowing, however, transnasal flexible fiberoptic laryngoscopy is not a frequently used airway assessment technique by anesthesiologists. As anesthesiologists, we continually deal with expected and unexpected difficult airways. Transnasal flexible fiberoptic laryngoscopy is one of the tools that we have recently started to use in patients in remote (outside the operating room [OR]) locations in collaboration with our otolaryngologist colleagues. We sometimes use the transnasal flexible fiberoptic laryngoscopy technique in conjunction with our otolaryngology colleagues in the emergency room, at other times in the ear-nose-throat clinic, and rarely in the preoperative holding area. This easy-to-use fiberoptic laryngoscopic technique helps us to make definitive management plans in potentially difficult airway cases including traumatized airway cases and airway malignancies. In this month’s issue of Anesthesia & Analgesia, Dr. Rosenblatt et al. present a very interesting airway article. The investigators used this technique to guide their airway assessment and anesthesia induction plans. They sought to determine whether preoperative (nasal) endoscopic airway evaluation (PEAE) affected airway management in patients with known upper airway pathology. The authors used transnasal flexible fiberoptic laryngoscopy to assess the upper airway down to the glottis, and concluded that PEAE affected their airway management in 26% of the patients. In a great majority of patients, PEAE supported decreased use of awake fiberoptic intubation, which possibly decreased anesthesia care time, increased patient comfort, and overall diminished the level of invasiveness. In a smaller percentage, PEAE emphasized the need for awake fiberoptic intubation, although the initial plan called for direct laryngoscopy after induction of general anesthesia. In addition to bringing the practical use of transnasal flexible fiberoptic laryngoscopy to our preoperative holding area, Dr. Rosenblatt et al. relayed a very important message in their article: transnasal fiberoptic laryngoscopy improves the safety of managing both our known and unpredictably difficult airway patients. We thus recommend that the reader focus more on the patient safety outcome obtained in the 8 patients in whom an awake tracheal intubation was not planned initially (false negatives), but who underwent awake intubation after PEAE. We believe that this benefit has a higher priority outcome compared with the potential benefit of improved patient comfort achieved from canceling awake intubation plans in 28 cases after PEAE (false positives). As the difficult airway team instructors, we believe that awake intubation is probably one of the most important skills that an anesthesiologist needs to master. The fear of potential patient discomfort (associated with awake fiberoptic attempts) should not supersede the critical safety measure gained by From the *Department of Anesthesiology & Perioperative Medicine, Neuroscience Intensive Care Unit, University of Louisville, Louisville, Kentucky; and †Outcomes Research Consortium.