Jeong Jin Lee

Postconditioning with isoflurane reduced ischemia-induced brain injury in rats.

Background:Preexposure of brain to isoflurane, a commonly used anesthetic, induces ischemic tolerance. This phenomenon is called isoflurane preconditioning. However, it is not known whether isoflurane application after ischemia provides neuroprotection. Methods:Corticostriatal slices (400 &mgr;m) freshly prepared from adult male Sprague-Dawley rats were subjected to a 15-min oxygen–glucose deprivation (OGD; to simulate ischemia in vitro). Isoflurane was applied after OGD. Brain slices were harvested 2 h after OGD for measuring 2,3,5-triphenyltetrazolium chloride (TTC) conversion to quantify cell injury. Adult male Sprague-Dawley rats were also subjected to middle cerebral arterial occlusion for 90 min and then treated with or without 2% isoflurane for 60 min started at the onset of reperfusion. The infarct volumes, neurologic deficit scores, and performance on rotarod were evaluated at 24 h after the onset of reperfusion. Results:Isoflurane applied immediately after the 15-min OGD for 30 min dose-dependently reversed the OGD-induced decrease of TTC conversion. The TTC conversion was 34 ± 16% and 58 ± 28% of the control, respectively, for OGD alone and OGD plus 2% isoflurane (P < 0.05, n = 12). Application of 2% isoflurane for 30 min started at 10 min after the OGD also reduced the OGD-decreased TTC conversion. The presence of 0.3 &mgr;m glibenclamide, a general adenosine 5′-triphosphate–sensitive potassium channel blocker, or 500 &mgr;m 5-hydroxydecanoic acid, a mitochondrial adenosine 5′-triphosphate–sensitive potassium channel blocker, during the application of 2% isoflurane abolished the isoflurane preservation of TTC conversion. Application of isoflurane during reperfusion also improved neurologic outcome after brain ischemia. Conclusions:The results suggest that isoflurane administrated after OGD or brain ischemia provides neuroprotection. Mitochondrial adenosine 5′-triphosphate–sensitive potassium channels may be involved in this protection.

Incidence of severe ventricular arrhythmias during pulmonary artery catheterization in liver allograft recipients

Liver allograft recipients may develop a hyperdynamic circulation and cardiac electrophysiologic abnormalities. The incidence of severe ventricular arrhythmias in liver allograft recipients during pulmonary artery (PA) catheterization was determined. One hundred five liver allograft recipients were studied prospectively; 5 of the patients with preexisting valvular heart disease, ischemic heart disease, or arrhythmias were excluded. Severe ventricular arrhythmia, defined as 3 or more consecutive ventricular premature beats occurring at a rate of >100 per minute, was observed in 37.0% of the patients during insertion of the catheter and in 25.0% of the patients during removal of the catheter. Two patients developed ventricular tachycardia, and 2 developed ventricular fibrillation; the arrhythmias in these 4 patients did not respond to appropriate pharmacological treatment but resolved promptly after removal of the PA catheter. The catheter transit time from the right ventricle to the pulmonary capillary wedge position was longer in patients with severe ventricular arrhythmia than in those without this arrhythmia (91.6 ± 103.6 s versus 53.3 ± 18.4 s, P < 0.05). In conclusion, patients undergoing liver transplantation have a high risk of developing a ventricular arrhythmia during PA catheterization. Liver Transpl 13:1451–1454. 2007.

Reactive oxygen species by isoflurane mediates inhibition of nuclear factor κB activation in lipopolysaccharide-induced acute inflammation of the lung.

BACKGROUND:Although anesthetic-induced inhibition of lipopolysaccharide (LPS)-induced lung injury has been recognized, the underlying mechanism is obscure. Some studies suggest that reactive oxygen species (ROS) by isoflurane play a crucial role for anesthetic-induced protective effects on the brain or the heart; however, it still remains controversial. In this study, we examined the role of isoflurane-derived ROS in isoflurane-induced inhibition of lung injury and nuclear factor &kgr;B (NF&kgr;B) activation in LPS-challenged rat lungs. METHODS:Male Sprague-Dawley rats were subjected to inhalation of 1.0 minimum alveolar concentration of isoflurane for 60 minutes, and intratracheal LPS 0.1 mg was administered 60 minutes later. In some cases, ROS scavenger, 2-mercaptopropinyl glycine or N-acetylcysteine was given 30 minutes before isoflurane. ROS generation was measured by fluorometer before LPS challenge and 4 hours after. Isoflurane’s preconditioning effect was assessed by histologic examination, protein content, neutrophil recruitment, and determination of tumor necrosis factor (TNF)-&agr;, interleukin (IL)-1&bgr;, and IL-6 levels in bronchoalveolar lavage fluid and lung tissue. Western blotting measured phosphorylation of inhibitory &kgr;B &agr; (ser 32/36), NF&kgr;B p65, and inducible nitric oxide synthase (iNOS). TNF-&agr; and IL-6 mRNA expression and immunofluorescence staining for iNOS were also assessed. RESULTS:Isoflurane preconditioning reduced inflammatory lung injury and TNF-&agr;, IL-1&bgr;, and IL-6 release in the lung. Isoflurane upregulated ROS generation before LPS but inhibited a ROS burst after LPS challenge. ROS scavenger administration before isoflurane abolished the isoflurane preconditioning effect as well as isoflurane-induced inhibition of phosphorylation of inhibitory &kgr;B&agr;, NF&kgr;B p65, iNOS activation, and mRNA expression of TNF-&agr; and IL-6 in acute LPS-challenged lungs. CONCLUSIONS:This study suggests a crucial role of upregulated ROS generation by isoflurane for modification of inflammatory pathways by isoflurane preconditioning in acute inflammation of the lung.

Effect of intraoperative lidocaine on anesthetic consumption, and bowel function, pain intensity, analgesic consumption and hospital stay after breast surgery

Background Perioperative lidocaine infusion improves postoperative outcomes, mostly after abdominal and urologic surgeries. Knowledge of the effect of lidocaine on peripheral surgeries is limited. Presently, we investigated whether intraoperative lidocaine infusion reduced anesthetic consumption, duration of ileus, pain intensity, analgesic consumption and hospital stay after breast plastic surgeries. Methods Sixty female patients, aged 20-60 years, enrolled in this prospective study were randomly and equally divided to two groups. One group (n = 30) received a 1.5 mg/kg bolus of lidocaine approximately 30 min before incision followed by continuous infusion of lidocaine (1.5 mg/kg/h) until skin closure (lidocaine group). The other group (n = 30) was untreated (control group). Balanced inhalation (sevoflurane) anesthesia and multimodal postoperative analgesia were standardized. End tidal sevoflurane concentration during surgery, time to the first flatus and defecation, visual analog pain scale (0-10), analgesic consumption and associated side effects at 24, 48, and 72 h after surgery, hospital stay, and patients general satisfaction were assessed. Results Compared to the control group, intraoperative lidocaine infusion reduced by 5% the amount of sevoflurane required at similar bispectral index (P = 0.014). However, there were no significant effects of lidocaine regarding the return of bowel function, postoperative pain intensity, analgesic sparing and side effects at all time points, hospital stay, and level of patients satisfaction for pain control. Conclusions Low dose intraoperative lidocaine infusion offered no beneficial effects on return of bowel function, opioid sparing, pain intensity and hospital stay after various breast plastic surgeries.

Improvement of sleep-related breathing disorder in patients with end-stage renal disease after kidney transplantation

Lee JJ, Kim GS, Kim JA, Kim S‐J, Kang JG, Kim GH, Jung HH. Improvement of sleep‐related breathing disorder in patients with end‐stage renal disease after kidney transplantation. 
Clin Transplant 2011: 25: 126–130.

The hemostatic profiles of patients with type O and non-O blood after acute normovolemic hemodilution with 6% hydroxyethyl starch (130/0.4)

BACKGROUND:Individuals with Type O blood have been reported to have a tendency toward reduced Factor VIII and von Willebrand Factor (vWF) levels. If this is true, patients with Type O blood might be vulnerable to coagulopathy during acute normovolemic hemodilution using hydroxyethyl starch (HES), both from hemodilution as well as HES-related coagulopathy. METHODS:Thirty non-O and 15 type O ASA 1 or 2 patients scheduled for spinal surgery involving more than two spinal levels were enrolled for the study. After anesthesia induction, 30% of the estimated blood volume was removed, and the volume was simultaneously replaced with 6% HES (130/0.4). Coagulation profiles were measured before (T0) and 30 min after acute normovolemic hemodilution (T30). RESULTS:Factor VIII activity, vWF antigen levels (vWF:ag), and vWF ristocetin cofactor activity (vWF:RCof) were lower in the O group than in the non-O group before and after acute normovolemic hemodilution, and decreased below the normal range in the O group after acute normovolemic hemodilution. The decrease was beyond that expected from hemodilution alone. Maximum amplitude and coagulation index of the thromboelastogram decreased below the normal range in the O group after acute normovolemic hemodilution. The decrease in vWF:ag was related to the degree of blood loss, and was greater in patients in the O group. CONCLUSIONS:Patients with Type O blood may have increased coagulation compromise, and greater dilution of Factor VIII activity, vWF:ag, and vWF:RCof after acute normovolemic hemodilution with HES.

Effect of preoperative skull block on pediatric moyamoya disease

OBJECT Stable hemodynamics, normocapnia, and adequate pain relief are considered important factors in the reduction of neurological complications in pediatric patients undergoing encephaloduroarteriomyosynangiosis (EDAMS) operations for the treatment of moyamoya disease. A preoperative skull block may reduce hemodynamic fluctuations and hypo- or hyperventilation due to emergence delirium or oversedation and provide adequate pain relief, thereby reducing postoperative morbidity. METHODS Pediatric patients (age 3-13 years) undergoing EDAMS surgery for moyamoya disease were randomly divided into a nerve block (NB) group (18 cases) or control group (21 cases). The treatment group patients received a preoperative NB (0.25% 5-8 ml bupivacaine mixed with 20-40 mg methylprednisolone) targeting the supraorbital, supratrochlear, auriculotemporal, and posterior auricular nerves. Patients in the control group did not receive NB. General anesthesia with sevoflurane was induced in both groups. RESULTS In the NB group, stable hemodynamic parameters were obtained with a lower sevoflurane concentration than in the control group. For delirious awakening, the odds ratio in the control group was 4.9 compared with the NB group. Pain and analgesic requirement were higher in the control patients than in the NB-treated patients during the postanesthesia care unit stay. However, the arterial CO(2) tension in the postanesthesia care unit did not differ between the 2 groups. The odds ratio in the control group for the rate of morbidity (cerebral infarction and reversible ischemic neurological deficits) during the first 24 hours following the operation was 3.2 compared with the NB group. CONCLUSIONS The use of skull block during EDAMS surgery provided easy hemodynamic control, calm awakening, and better pain relief and may be related to the reduced postoperative morbidity.

Anesthetic management of awake craniotomy with laryngeal mask airway and dexmedetomidine in risky patients

Awake craniotomy is the technique of choice for the patients with lesions on eloquent cortical areas. It is still challenging for anesthesiologists, especially in cases where the patient’s general condition is poor or with a relatively inexperienced surgeon. Occasionally the inability to control airway can lead to complications such as airway obstruction or hypercarbia, which can lead to brain bulging. Different anesthetic combinations have been reported for awake craniotomy. Nevertheless, there is still no consensus about the optimal regimen for awake craniotomy [1]. We experienced six patients with fronto-temporal lesion who needed awake surgery to preserve eloquent areas. Two patients had cardiac problems and one patient had chronic depression (Table 1). All patients received scalp nerve block with 0.75% ropivacaine and 1 : 200,000 epinephrine. Three of the patients under went “asleep-awake” technique using a laryngeal mask airway (LMA). The other patients received moderate to mild sedation. We used propofol and remifentanil infusion for sedation and two patients received dexmedetomidine infusion as an adjuvant. We did not use muscle relaxants in any cases. Mean operation time was 323 minutes and estimated blood loss was 380 ml. One patient with severe snoring refused sedation at first and stayed fully awake until the end of cortical mapping. This patient displayed marked agitation during the awake period. Therefore, we started low dose propofol-remifentanil infusion after cortical mapping and the patient underwent intermittent apnea and hypercarbia (Patient 1). Most of the patients were maintained in a sedated state during the procedures and responded properly during cortical mapping. Two patients with LMA awakened 20-30 min after stopping infusion (Patients 2 and 3), and one (Patient 3) showed moderate hypercarbia. Other patients awakened within 10 min after stopping infusion. Surgeons were satisfied with patient’s brain condition and response. One patient (Patient 5) with moderate sedation experienced extreme fear during the procedure. Others replied that it was endurable. Awake craniotomy is very stressful surgery to patients. Although it is not always consistent, there is a greater possibility of extreme fear in the patients with prior anxiety history (e.g., Patient 5). Patients with medical problems, especially with cardiovascular diseases, may not tolerate the stressful environment and may lead to hemodynamic instability. In such cases, deep sedation is preferred. According to other references, most painful procedures were head pin fixation, manipulating dura, and closure after operation. Patients can easily get stressed during these procedures despite successful scalp nerve block [2]. Therefore, maintaining deep sedation or general anesthetic status during these procedures would be more helpful for patients’ comfort. The most important problem of deep sedation is respiratory depression, and using airway device such as LMA may be a good choice [3]. But, it can also cause delayed awake and some residual effects with dull response or respiratory depression after extubation (e.g., Patients 2 and 3). Hypercarbia brings increased intracranial pressure in spite of normal oxygen saturation, and it can make the surgery harder. Yet, in practice, LMA re-insertion after neurologic test is very dangerous owing to head fixation posture.

Exposure of isoflurane-treated cells to hyperoxia decreases cell viability and activates the mitochondrial apoptotic pathway

Isoflurane has either neuroprotective or neurotoxic effects. High-dose oxygen is frequently used throughout the perioperative period. We hypothesized that hyperoxia will affect cell viability of rat pheochromocytoma (PC12) cells that were exposed to isoflurane and reactive oxygen species (ROS) may be involved. PC12 cells were exposed to 1.2% or 2.4% isoflurane for 6 or 24h respectively, and cell viability was evaluated. To investigate the effects of hyperoxia, PC12 cells were treated with 21%, 50%, or 95% oxygen and 2.4% isoflurane for 6h, and cell viability, TUNEL staining, ROS production, and expression of B-cell lymphoma 2 (BCL-2), BCL2-associated X protein (BAX), caspase-3 and beta-site APP cleaving enzyme (BACE) were measured. ROS involvement was evaluated using the ROS scavenger 2-mercaptopropiopylglycine (MPG). The viability of cells exposed to 2.4% isoflurane was lower than that of cells exposed to 1.2% isoflurane. Prolonged exposure (6h vs. 24h) to 2.4% isoflurane resulted in a profound reduction in cell viability. Treatment with 95% (but not 50%) oxygen enhanced the decrease in cell viability induced by 2.4% isoflurane alone. Levels of ROS, Bax, caspase-3 and BACE were increased, whereas expression of Bcl-2 was decreased, in cells treated with 95% oxygen plus 2.4% isoflurane compared with the control and 2.4% isoflurane plus air groups. MPG attenuated the effects of oxygen and isoflurane. In conclusion, isoflurane affects cell viability in a dose- and time-dependent manner. This effect is augmented by hyperoxia and may involve ROS, the mitochondrial apoptotic signaling pathway, and β-amyloid protein.

Effects of partial neuromuscular blockade on lateral spread response monitoring during microvascular decompression surgery

OBJECTIVE We evaluated the effect of partial neuromuscular blockade (NMB) and no NMB on successful intraoperative monitoring of the lateral spread response (LSR) during microvascular decompression (MVD) surgery. METHODS Patients were randomly allocated into one of three groups: the TOF group, the NMB was targeted to maintain two counts of train-of-four (TOF); the T1 group, maintain the T1/Tc (T1: amplitude of first twitch, Tc: amplitude of baseline twitch) ratio at 50%; and the N group, no relaxants after tracheal intubation. Successful LSR monitoring was defined as effective baseline establishment and maintenance of the LSR until dural opening. RESULTS The success rate of LSR monitoring was significantly lower in the TOF group. But, there was no significant difference between T1 and N. The detection rate of spontaneous free-run electromyography (EMG) activity was significantly higher in the N group compared with the TOF and T1 groups. CONCLUSIONS Partial NMB with a target of T1/Tc ratio at 50% allows good recording of LSR with same outcome as surgery without NMB, and reduced spontaneous EMG activity. SIGNIFICANCE We suggested the availability of partial NMB for intraoperative LSR monitoring.