Eugene S. Fu

Preemptive Ketamine Decreases Postoperative Narcotic Requirements in Patients Undergoing Abdominal Surgery

The aim of this study was to determine if preemptive administration of systemic ketamine decreases postoperative pain when compared with postwound closure administration of ketamine.Patients undergoing abdominal procedures were randomized into a preemptive or postwound closure ketamine administration group. Before surgical incision, patients in the preemptive group (n = 20) were given 0.5 mg/kg ketamine followed by a ketamine infusion of 10 micro g [centered dot] kg-1 [centered dot] min-1, which was discontinued at abdominal closure. The patients in the postwound closure (n = 20) group were given 0.5 mg/kg of ketamine immediately after abdominal closure. Postoperatively, all patients received intravenous (IV) morphine in the postanesthesia care unit (PACU) and were started on IV morphine patient-controlled analgesia after discharge from the PACU. Postoperative pain was assessed by measuring morphine consumption and visual analog scale (0-100 mm) pain scores at rest. Patients in the preemptive group had significantly lower morphine consumption on postoperative Days 1 and 2. No significant intergroup differences were seen in the pain scores throughout the study period. Preemptive ketamine decreased postoperative opioid requirements, which was observed long after the normal expected duration of ketamine. (Anesth Analg 1997;84:1086-90)

Human Umbilical Cord Blood Stem Cells Infusion in Spinal Cord Injury: Engraftment and Beneficial Influence on Behavior

The use of human umbilical cord blood (hUCB)--a rich source of nonembryonic or adult stem cells--has recently been reported to ameliorate behavioral consequences of stroke. In this study, we tested whether human cord blood leukocytes also ameliorate behavioral impairments of spinal cord injury. Rats were divided into five groups: (1) laminectomy (without spinal cord injury) only; (2) laminectomy + cord blood infusion; (3) spinal cord injury + cord blood infused 1 day post injury; (4) spinal cord injury + cord blood infused 5 days post injury; and (5) spinal cord injury only. Spinal cord injury was induced by compressing the spinal cord for 1 min with an aneurysm clip calibrated to a closing pressure of 55 g. Open-field behavior was assessed 1, 2, and 3 weeks after intravenous injection of prelabeled human cord blood cells. Open-field test scores of spinal cord injured rats treated with human cord blood at 5 days were significantly improved as compared to scores of rats similarly injured but treated at day 1 as well as the otherwise untreated injured group. The results suggest that cord blood stem cells are beneficial in reversing the behavioral effects of spinal cord injury, even when infused 5 days after injury. Human cord blood-derived cells were observed in injured areas, but not in noninjured areas, of rat spinal cords, and were never seen in corresponding areas of spinal cord of noninjured animals. The results are consistent with the hypothesis that cord blood-derived stem cells migrate to and participate in the healing of neurological defects caused by traumatic assault.

Capnography accurately detects apnea during monitored anesthesia care

Apnea and airway obstruction are common during monitored anesthesia care (MAC). Because their early detection is essential, we sought to measure the efficacy of capnography as an indicator of apnea during MAC at a variety of oxygen flow rates compared with thoracic impedance. Anesthesia care providers using standard American Society of Anesthesiologists monitors were blinded to capnography and thoracic impedance monitoring. Ten (26%) of the 39 patients studied developed 20 s of apnea; none was detected by the anesthesia provider, but all were detected by capnography and impedance monitoring. There was no difference in detection rates between the two methods. Higher oxygen flow rates decreased the amplitude of the capnograph but did not interfere with apnea detection. This pilot study revealed that apnea of at least 20 s in duration may occur in every fourth patient undergoing MAC. Although these episodes were undetected by the anesthesia provider, they were reliably detected by both capnography and respiratory plethysmography. Monitoring of nasal end-tidal CO2 is an important way to improve safety in patients undergoing MAC.

Transgenic Inhibition of Glial NF-kappa B Reduces Pain Behavior and Inflammation after Peripheral Nerve Injury

&NA; The transcription factor nuclear factor kappa B (NF‐&kgr;B) is a key regulator of inflammatory processes in reactive glial cells. We utilized a transgenic mouse model (GFAP‐I&kgr;B&agr;‐dn) where the classical NF‐&kgr;B pathway is inactivated by overexpression of a dominant negative (dn) form of the inhibitor of kappa B (I&kgr;B&agr;) in glial fibrillary acidic protein (GFAP)‐expressing cells, which include astrocytes, Schwann cells, and satellite cells of the dorsal root ganglion (DRG) and sought to determine whether glial NF‐&kgr;B inhibition leads to a reduction in pain behavior and inflammation following chronic constriction injury (CCI) of the sciatic nerve. As expected, following CCI nuclear translocation, and hence activation, of NF‐&kgr;B was detected only in the sciatic nerve of wild type (WT) mice, and not in GFAP‐I&kgr;B&agr;‐dn mice, while upregulation of GFAP was observed in the sciatic nerve and DRGs of both WT and GFAP‐I&kgr;B&agr;‐dn mice, indicative of glial activation. Following CCI, mechanical and thermal hyperalgesia were reduced in GFAP‐I&kgr;B&agr;‐dn mice compared to those in WT, as well as gene and protein expression of CCL2, CCR2 and CXCL10 in the sciatic nerve. Additionally, gene expression of TNF, CCL2, and CCR2 was reduced in the DRGs of transgenic mice compared to those of WT after CCI. We can therefore conclude that transgenic inhibition of NF‐&kgr;B in GFAP‐expressing glial cells attenuated pain and inflammation after peripheral nerve injury. These findings suggest that targeting the inflammatory response in Schwann cells and satellite cells may be important in treating neuropathic pain.

A prospective, randomized, double-blind comparison of epidural and intravenous sufentanil infusions.

BackgroundThe site of action (spinal vs. central) of epidurally administered lipid-soluble opioids has been the subject of controversy. We compared the efficacy, plasma concentration and side effects of epidural and intravenously administered sufentanil for postoperative pain relief. MethodsUsing a double-blind, prospective design, 50 patients scheduled for intraabdominal operations during combined epidural-general anesthesia were randomized into one of two groups. Patients in group 1 (n = 24) received a 1-μg/ml sufentanil infusion epidurally at 0.2 μg · kg−1. h−1 and a saline infusion intravenously at the same rate. Patients in group 2 (n = 26) received a 1-μg/ml sufentanil infusion intravenously at 0.2 μg · kg−1. h−1 and a saline infusion epidurally at the same rate. Intravenous morphine sulfate was available in 2-mg increments to all patients in the postanesthesia care unit until visual analogue scale (0–100 mm) pain score was ≤30. Then, a patient-controlled intravenous pump providing morphine on demand (1 mg with a 10-min lockout) was begun. Blood samples were drawn for sufentanil plasma levels and patients were assessed for pain, sedation and nausea for the 48 h after commencement of the infusions. ResultsSimilar visual analogue pain, sedation, and nausea scores were found between the patients in the two groups. No differences were found in supplemental morphine requirements and plasma sufentanil concentrations between the patients in the two groups. A higher incidence of excessive sedation requiring infusion decrease was infusion decrease was found in the intravenous group (six vs. one, P < 0.05). ConclusionsMany clinical similarities were found when epidural and intravenous sufentanil infusions were compared. The higher incidence of excessive sedation in the patients receiving intravenous sufentanil could not be explained on the basis of plasma sufentanil concentrations alone. This study indicates that little clinical difference exists between epidural and intravenous administration of sufentanil.

Methylprednisolone inhibits production of interleukin-1beta and interleukin-6 in the spinal cord following compression injury in rats.

Interleukin-1β (IL-1β) and interleukin-6 (IL-6) are major inflammatory cytokines produced after spinal cord injury (SCI). This study sought to evaluate the effects of methylprednisolone (MP) on IL-1β and IL-6 protein in spinal cord tissue following SCI. Halothane-anesthetized, female Sprague-Dawley rats weighing (280-320 g) underwent laminectomy at T7-T8. No lesions were produced in animals in the saline control and MP control groups. SCI was induced by temporary placement of an aneurysm clip at T7-T8, with a closing pressure of 55 g at the spinal level of T7-T8, resulting in spinal cord compression for one minute. Animals with SCI were treated with MP (30 mg/kg sc) or an equal volume of saline. IL-1β and IL-6 spinal cord protein were measured by enzyme-linked immunosorbent assays (ELISA). Data were summarized as mean ± SD and compared by two-way analysis of variance (ANOVA). IL-1β and IL-6 levels were elevated in the SCI + Saline animals (P < 0.01) compared with saline control, MP control, and SCI + MP-treated animals. The rise in IL-1β and IL-6 levels after SCI was blunted after administration of MP, suggesting an interaction between glucocorticosteroids and the cytokine cascade after spinal cord trauma. Further evaluation of the effects of MP on the cytokine cascade may be important in assessing whether or not the anti-inflammatory effects of glucocorticosteroids confer neuroprotection after SCI.

Neuroprotection in brain and spinal cord trauma.

Purpose of review Traumatic brain and spinal cord injuries continue to be a public health problem. These types of injuries often occur in early adulthood and have a major impact for society. This review discusses strategies and therapeutic agents for perioperative neuroprotection in the management of brain and spinal cord trauma. Recent findings There are no definitive drugs or strategies that can be utilized to provide perioperative neuroprotection in brain and spinal cord trauma patients. Phase III trials of several pharmacologic agents, including inhibitors of oxidative and excitotoxic injury, have been unable to demonstrate clinical efficacy. Although experimental animal data for hypothermia have been promising over the years, clinical application of therapeutic hypothermia cannot be recommended for routine use in neurotrauma patients. Administration of methylprednisolone, which has become common practice in acute spinal cord injury, has come under close scrutiny. Various experimental animal investigations suggest that potential therapeutic agents include estrogen, progesterone, minocycline, erythropoietin, and magnesium. Summary The main priority in the initial treatment of brain and spinal cord trauma is to maintain oxygenation and perfusion in order to avoid aggravating secondary injury. Future progress will depend on the translation of neuroprotective strategies into well designed clinical trials with promising outcomes.

Forearm compartment syndrome from intravenous mannitol extravasation during general anesthesia.

IMPLICATIONS Complications of IV mannitol administration resulting in compartment syndrome may warrant surgical intervention. Compartment syndrome is difficult to diagnose in the anesthetized patient. Infusing mannitol in an observed IV site permits discontinuation of mannitol before complications ensue. Early recognition and surgical intervention averted potential impairment in our patient.

Malignant hyperthermia involving the administration of desflurane

PurposeThis report describes an episode of malignant hyperthermia (MH) in a ten year old boy receiving desflurane anaesthesia.Clinical featuresFollowing induction of general endotracheal anaesthesia with thiopentone and succinylcholine, desflurane was administered for maintenance of anaesthesia. Ten minutes after commencing desflurane administration, heart rate andPetCO2 increased to 165 bpm and 50 mmHg, respectively. Initially, the tachycardia was attributed to a sympathetic response secondary to desflurane. Desflurane was discontinued and isoflurane was started. Minute ventilation was increased to decreasePetCO2-Over the next five minutes, temperature increased to 38.4°C as thePetCO2 increased to above 60 mmHg. Venous and arterial blood gases were drawn which showed acidosis and hypercapnia. Temperature andPetCO2 continued to increase, reaching peak values of 41°C and 77 mmHg, respectively. Efforts to cool the patient were made. A total of 220 mg dantrolene sodium was administered iv. Following dantrolene, the temperature increase and acidosis subsided. Heart rate andPetCO2 decreased to 130 bpm and 36 mmHg, respectively. The surgical procedure was expeditiously performed. Postoperatively, in the Paediatric Intensive Care Unit, a dantrolene infusion of 20 mg · hr−1 was administered for 12 hr. The trachea was extubated the following morning. Several days later, the patient underwent another surgical procedure without complications using MH-safe anaesthetics.ConclusionOnset of tachycardia in a patient receiving desflurane may initially be attributed to desflurane-induced sympathetic hyperactivity. This poses a clinical challenge in the diagnosis of MH during desflurane anaesthesia.RésuméObjectifCommuniquer le compte rendu d’un épisode d’hyperthermie (HM) survenu chez un enfant de dix ans anesthésié au desflurane.Caractéristiques cliniquesAprès l’induction d’une anesthésie générale endotrachéale avec du thiopentone et de la succinylcholine, du desflurane a été administré pour l’entretien de l’anesthésie. Deux minutes après le début de l’administration de cet agent, la fréquence cardiaque et lePetCO2 ont respectivement augmenté à 165 bpm et 50 mmHg. Initialement, la tachycardie a été attribuée à une réaction sympathique provoquée par le desflurane. Pendant les cinq minutes suivantes, la température a augmenté à 38,4°C et laPetCO2 a dépassé 60 mmHg. Des échantillons de sang artériel et veineux ont révélé la présence d’acidose et d’hypercapnie. La température et laPetCO2 ont continué d’augmenter à des valeurs maximales respectives de 41 °C et 77 mmHg. Des manoeuvres de refroidissement ont été entreprises. Une dose totale de 220 mg de dantrolène sodique a été administrée par la voie veineuse. La température et l’acidose se sont stabilisées. La fréquence cardiaque et laPetCO2 ont baissé respectivement à 130 bpm et 36 mmHg. L’intervention a été terminée rapidement. En postopératoire, à l’unité des soins intensifs pédiatriques, une perfusion de dantrolène 20 mg · h−1 a été administrée pendant 12 h. La trachée a été extubée le lendemain matin. Quelques jours plus tard, le patient a subi une autre intervention chirurgicale sous anesthésie ne comportant pas d’agents déclenchants de l’HM.ConclusionSous desflurane, il est possible d’attribuer un accès de tachycardie à l’hyperactivité sympathique. Ceci peut compliquer le diagnostic de l’HM.

Transgenic glial nuclear factor-kappa B inhibition decreases formalin pain in mice

In this work, we studied transgenic glial fibrillary acidic protein-IκB&agr;-dn mice that selectively inactivate the classical nuclear factor κB pathway by overexpressing the inhibitory protein of κB&agr; in astrocytes, under the control of glial fibrillary acidic protein promoter. We sought to determine if glial nuclear factor κB inhibition decreases formalin pain. Formalin testing was carried out on 25–35 g littermate adult male wild-type and transgenic C57Bl/6 mice. Formalin increased spinal cord c-Fos expression and glial fibrillary acidic protein immunostaining in both wild-type and transgenic mice. Transgenic glial fibrillary acidic protein-inhibitory protein of κB&agr;-dn mice had lower duration of formalin-induced paw-licking behavior. These data support a role of glial nuclear factor κB inhibition in reducing pain after peripheral nerve inflammation.