A randomized comparison of three intubation techniques/tube materials for nasotracheal intubation.

PURPOSE: We sought to compare three intubation methods using different intubation techniques/tube materials for tube advancement from the nasal cavity into the oral cavity during nasotracheal intubation. METHODS: We conducted a randomized clinical trial with adult patients scheduled to undergo elective surgery requiring nasotracheal intubation for general anesthesia. Participants were randomly allocated to a polyvinyl chloride (PVC) tube group (group P), PVC tube attached to a rubber catheter group (group PR), or velvet-soft PVC tube group (group V). Tracheal intubation was then performed based on group allocation. The primary outcome was the first-attempt success rate of tube advancement into the oral cavity; secondary outcomes included the time required for tube advancement into the oral cavity, total intubation time, and the incidence of epistaxis. RESULTS: A total of 149 patients were included in the study. The first-attempt success rate in group V (90%) was significantly higher than that in group P (58%) (odds ratio, 6.5; 95% confidence interval [CI], 2.2 to 19.2), but similar to that in group PR (100%). The mean (standard deviation) time required for tube advancement into the oral cavity was significantly shorter in group V (16 [13] sec) than in group PR [40 (10) sec; 95% CI of mean difference, 17 to 30] and group P (26 [16] sec; 95% CI of mean difference, 3 to 16). Total intubation time was longest in group PR. Epistaxis occurred the least in group V. CONCLUSIONS: Among the three intubation techniques/tube materials for nasotracheal intubation, the velvet-soft PVC tube provided the highest first-attempt success rate, most expeditious advancement into the oral cavity, and lowest incidence of epistaxis. STUDY REGISTRATION: ClinicalTrials.gov (NCT04695444); first submitted 30 December 2020.

RéSUMé: OBJECTIF: Nous avons cherché à comparer trois méthodes d'intubation utilisant différentes techniques d'intubation / matériaux de sondes pour l'avancement de la sonde de la cavité nasale dans la cavité buccale pendant l'intubation nasotrachéale. MéTHODE: Des patient·es devant recevoir une intubation nasotrachéale ont été réparti·es au hasard dans un groupe avec sondes en polychlorure de vinyle (PVC) (groupe P), un groupe avec sondes en PVC attachées à un cathéter en caoutchouc (groupe PR) ou un groupe avec sondes en PVC doux comme du velours (groupe V). L'intubation trachéale a ensuite été réalisée en fonction de l'affectation du groupe. Le critère d'évaluation principal était le taux de réussite de la première tentative d'avancement de la sonde dans la cavité buccale; les critères d'évaluation secondaires comprenaient le temps nécessaire à l'avancement de la sonde dans la cavité buccale, la durée totale de l'intubation et l'incidence d'épistaxis. RéSULTATS: Au total, 149 patient·es ont été inclus·es dans l'étude. Le taux de réussite de l'intubation à la première tentative était significativement plus élevé dans le groupe V (90 %) que dans le groupe P (58 %) (rapport de cotes, 6,5; intervalle de confiance à 95 % [IC], 2,2 à 19,2), mais similaire à celui du groupe PR (100 %). Le temps moyen (écart type) nécessaire pour l'avancement de la sonde dans la cavité buccale était significativement plus court dans le groupe V (16 [13] sec) que dans le groupe PR (40 [10] sec; IC 95 % de la différence moyenne, 17 à 30) et dans le groupe P (26 [16] sec; IC 95 % de la différence moyenne, 3 à 16). La durée totale d'intubation était la plus longue dans le groupe PR. C'est dans le groupe V que l'épistaxis a été la moins fréquente. CONCLUSION: Parmi les trois techniques d'intubation/matériaux de sonde pour l'intubation nasotrachéale, le tube en PVC doux comme du velours a fourni le taux de réussite de première tentative le plus élevé, l'avancement le plus rapide dans la cavité buccale et l'incidence d'épistaxis la plus faible. ENREGISTREMENT DE L'éTUDE: ClinicalTrials.gov (NCT04695444); première soumission le 30 décembre 2020.

Aprepitant for antiemesis after laparoscopic gynaecological surgery: A randomised controlled trial.

BACKGROUND: Ondansetron, a 5-HT3 receptor antagonist, and aprepitant, a neurokinin-1 receptor antagonist, block the emetic effect of serotonin and neurokinin, respectively. Aprepitant combined with ondansetron can be more effective for preventing emesis in patients at high risk of postoperative nausea and vomiting (PONV). OBJECTIVE: To investigate the prophylactic effect of combining aprepitant with ondansetron compared with ondansetron alone on PONV in patients with fentanyl-based patient-controlled analgesia (PCA) after laparoscopic gynaecological surgery. DESIGN: Single-centre, double-blinded randomised controlled trial. SETTING: A major university hospital in Seoul, Korea, between July 2012 and April 2013. PATIENTS: One hundred and twenty-five female patients (American Society of Anesthesiologists' physical status 1 or 2) with fentanyl-based intravenous PCA after gynaecological laparoscopy were recruited to the study, and 110 completed the protocol. INTERVENTIONS: Oral aprepitant 80 mg or placebo was given 1 h before anaesthesia. In all patients, ondansetron 4 mg was administered intravenously at the end of surgery and 12 mg was added to the PCA solution. MAIN OUTCOME MEASURES: The primary outcome measure was complete response (no PONV and no rescue antiemetics) up to 48 h postoperatively. RESULTS: There was no difference in the proportion of complete responses to 48 h between the groups (P = 0.05), but in the post-anaesthesia care unit and up to 24 h postoperatively, the proportion was significantly higher in the aprepitant and ondansetron group than in the ondansetron only group (76 vs. 50%, P = 0.004 and 38 vs. 16%, P = 0.011, respectively). In the aprepitant and ondansetron group, the time to first PONV was delayed (P = 0.014) and the incidence of nausea up to 24 h postoperatively was lower (P = 0.014). However, there were no differences in the incidences of retching or vomiting, the severity of nausea, use of rescue antiemetics or the incidence of side-effects. CONCLUSION: Aprepitant 80 mg orally with ondansetron is effective in suppressing early PONV up to 24 h postoperatively and delays the time to first PONV in patients with fentanyl-based intravenous PCA after gynaecological laparoscopy. However, the combination prophylaxis with aprepitant and ondansetron failed to reach the predefined primary study outcome when compared with ondansetron alone. TRIAL REGISTRATION: Clinicaltrial.gov identifier: NCT01897337.

Efficacy of a single dose of dexmedetomidine for cough suppression during anesthetic emergence: a randomized controlled trial.

PURPOSE: Maintenance of a remifentanil infusion during anesthetic emergence has been reported to decrease the incidence of coughing and thereby help to ensure a smooth emergence. It may, however, cause respiratory depression and possibly delay emergence. The purpose of this study was to investigate the effect of a single dose of dexmedetomidine combined with a low-dose remifentanil infusion on cough suppression during emergence from general anesthesia. METHODS: American Society of Anesthesiologists physical status I-II adults undergoing elective thyroidectomy under sevoflurane anesthesia were recruited and randomly allocated to receive either dexmedetomidine 0.5 µg·kg(-1) iv (Group D, n = 70) or saline (Group S, n = 71), each combined with a low-dose remifentanil infusion ten minutes before the end of surgery. Coughing was assessed using a four-point scale. The respiratory rate (RR), heart rate (HR), and mean arterial pressure were also recorded. RESULTS: The incidence of coughing was lower in Group D than in Group S (64% vs 91%, respectively; mean difference 27%; 95% confidence interval [CI] 13 to 41; P < 0.001). The median cough grade at extubation was also lower in Group D. Mean arterial pressure and HR were elevated in Group S during tracheal extubation but were similar to baseline values in Group D. There was no difference in RR between the two groups throughout the study. A small delay in extubation was observed in Group D (3 minutes longer than Group S; 95% CI 2 to 4; P < 0.001). CONCLUSION: Compared with an infusion of low-dose remifentanil alone, the addition of a single dose (0.5 µg·kg(-1)) of dexmedetomidine during emergence from sevoflurane-remifentanil anesthesia was effective in attenuating coughing and hemodynamic changes and did not exacerbate respiratory depression after thyroid surgery. This trial was registered at Clinicaltrial.gov, identifier: NCT01774305.

Hyperglycemia attenuates myocardial preconditioning of remifentanil.

BACKGROUND: Hyperglycemia attenuates cardioprotection by remifentanil-preconditioning in ischemia-reperfusion in vivo in diabetic rats. However, the effects of hyperglycemia in cultured ventricular myocytes remains unknown. Therefore, we examined the in vitro effects of hyperglycemia on hypoxia-reoxygenation (H/R) and cardioprotection from remifentanil-preconditioning in isolated neonatal rat ventricular myocytes (NRVMs), including effects on apoptotic signaling pathways and Ca(2+) homeostasis. MATERIALS AND METHODS: NRVMs were cultured in medium with 5.5 mM (normoglycemia) or 25.5 mM glucose for one day. Then, NRVMs in H/R groups were exposed to 1 h of hypoxia and 5 h of reoxygenation with or without remifentanil-preconditioning at 1 µM. Cell viability, apoptosis, and Ca(2+) homeostasis were assessed by MTT assay, caspase-3 assay, confocal microscopy and immunoblots. RESULTS: In normoglycemia, remifentanil-preconditioning improved the viability of cardiomyocytes (P < 0.01) and prevented the increase of caspase-3 activity and Ca(2+) overload after H/R injury (P < 0.05). In addition, decrease in Akt, ERK1/2, and Bcl-2, and the increase in Bax by H/R was attenuated by remifentanil-preconditioning (P < 0.05). However, in hyperglycemia, the viability was partially impaired after H/R but not improved by remifentanil-preconditioning. Apoptotic activity, Ca(2+) concentration, and apoptotic kinases except Akt were not affected by either H/R or remifentanil-preconditioning under hyperglycemia. Akt phosphorylation was decreased by H/R but not restored by remifentanil preconditioning. CONCLUSIONS: Remifentanil preconditioning under normoglycemia renders NRVMs resistant to H/R injury by reducing apoptosis and intracellular Ca(2+) concentrations. The mechanism appears to be modulation of apoptotic signaling. However, hyperglycemia mitigates H/R injury in NRVMs, and may reduce the protective effect of remifentanil-preconditioning that may be associated with the Akt pathways.

Limited cryoablation reduces hospital stay and opioid consumption compared to thoracic epidural analgesia after minimally invasive repair of pectus excavatum.

pain following minimally invasive repair of pectus excavatum (MIRPE) is a critical concern that leads to a prolonged hospital stay and high doses of opiates administered to the patients. This study aimed to evaluate the efficacy of intraoperative cryoanalgesia (cryoablation of the intercostal nerves) during MIRPE. We retrospectively analyzed the data of 64 patients who underwent MIRPE and received cryoanalgesia or epidural analgesia between January 2019 and January 2021. The oral morphine milligram equivalent (MME) was used to calculate the dosage of opioid agents. The median age was 15 years (range, 4-33 years). The median postoperative hospital stay was 4 days (range, 2-6 days), with a median oral MME consumption of 45 mg (ranging from 0 to 1360 mg). Cryoanalgesia was performed in 38 patients, and epidural analgesia was administered to the remaining 26 patients. The cryoanalgesia group had a significantly lesser pain score, shorter postoperative hospital stay and lower oral MME consumption than the epidural analgesia group (5 vs 2; P < .001, 3 days vs 5 days; P < .001, 19 mg vs 634 mg; P < .001). Cryoanalgesia appears to reduce postoperative hospital stay and opioid consumption compared with epidural analgesia. The outcomes of this study indicate that cryoanalgesia might be a safe and effective method for pain control following MIRPE.

Isoflurane differentially modulates mitochondrial reactive oxygen species production via forward versus reverse electron transport flow: implications for preconditioning.

BACKGROUND: Reactive oxygen species (ROS) mediate the effects of anesthetic precondition to protect against ischemia and reperfusion injury, but the mechanisms of ROS generation remain unclear. In this study, the authors investigated if mitochondria-targeted antioxidant (mitotempol) abolishes the cardioprotective effects of anesthetic preconditioning. Further, the authors investigated the mechanism by which isoflurane alters ROS generation in isolated mitochondria and submitochondrial particles. METHODS: Rats were pretreated with 0.9% saline, 3.0 mg/kg mitotempol in the absence or presence of 30 min exposure to isoflurane. Myocardial infarction was induced by left anterior descending artery occlusion for 30 min followed by reperfusion for 2 h and infarct size measurements. Mitochondrial ROS production was determined spectrofluorometrically. The effect of isoflurane on enzymatic activity of mitochondrial respiratory complexes was also determined. RESULTS: Isoflurane reduced myocardial infarct size (40 ± 9% = mean ± SD) compared with control experiments (60 ± 4%). Mitotempol abolished the cardioprotective effects of anesthetic preconditioning (60 ± 9%). Isoflurane enhanced ROS generation in submitochondrial particles with nicotinamide adenine dinucleotide (reduced form), but not with succinate, as substrate. In intact mitochondria, isoflurane enhanced ROS production in the presence of rotenone, antimycin A, or ubiquinone when pyruvate and malate were substrates, but isoflurane attenuated ROS production when succinate was substrate. Mitochondrial respiratory experiments and electron transport chain complex assays revealed that isoflurane inhibited only complex I activity. CONCLUSIONS: The results demonstrated that isoflurane produces ROS at complex I and III of the respiratory chain via the attenuation of complex I activity. The action on complex I decreases unfavorable reverse electron flow and ROS release in myocardium during reperfusion.

Magnesium sulfate prevents remifentanil-induced postoperative hyperalgesia in patients undergoing thyroidectomy.

BACKGROUND: In a randomized, double-blind, prospective study, we investigated whether an intraoperative high versus low dose of remifentanil increased postoperative hyperalgesia and whether magnesium can prevent remifentanil-induced hyperalgesia. METHODS: Ninety patients undergoing thyroidectomy were randomly assigned to 1 of 3 groups. Remifentanil was intraoperatively infused at 0.05 µg/kg/min (group LO) or 0.2 µg/kg/min (groups HI and HM). Patients in group HM received MgSO(4) 30 mg/kg at induction followed by an intraoperative infusion of 10 mg/kg/h. Mechanical pain thresholds on the forearm and periincisional area were assessed by von Frey filament the evening before surgery and postoperatively at 24 and 48 hours. Pain measured on a verbal numerical rating scale (VNRS) (0-10) and additional analgesics were recorded in the postanesthesia care unit postoperatively at 6, 24, and 48 hours. RESULTS: There was a significantly greater decrease in pain threshold on the periincisional area at 24 and 48 hours postoperatively in group HI, as compared with the other 2 groups. The 95% confidence intervals for the mean difference in pain thresholds on the periincisional area at 24 and 48 hours postoperatively were 0.31 to 1.11 and 0.36 to 1.14 for group HI versus group LO, 0.45 to 1.26 and 0.54 to 1.32 for group HI versus group HM (values are log(10) of force in milligrams). The change in pain threshold on the forearm was similar among the groups. Group HI had significantly higher VNRS scores (median [interquartile range], 3 [2-4]) than group LO (2 [1-3] and group HM (2 [1-3]) at 48 hours postoperatively. The 95% confidence intervals for median difference in VNRS score at 48 hours postoperatively were 1 to 2 for group HI versus group LO and 0 to 2 for group HI versus group HM. There were no significant differences in the number of patients who requested rescue analgesics in the postoperative anesthesia care unit and general ward during 48 hours postoperatively among the 3 groups. CONCLUSIONS: A relatively high dose of intraoperative remifentanil enhances periincisional hyperalgesia. Intraoperative MgSO(4) prevents remifentanil-induced hyperalgesia. However, hyperalgesia did not reach clinical relevance in terms of postoperative pain or analgesic consumption in patients undergoing thyroidectomy.

Perioperative administration of pregabalin for pain after robot-assisted endoscopic thyroidectomy: a randomized clinical trial.

BACKGROUND: Perioperative administration of pregabalin, which is effective for neuropathic pain, might reduce early postoperative and chronic pain. This randomized, double-blinded, placebo-controlled trial (Clinical Trials.gov ID NCT00905580) was designed to investigate the efficacy and safety of pregabalin for reducing both acute postoperative pain and the development of chronic pain in patients after robot-assisted endoscopic thyroidectomy. METHODS: Ninety-nine patients were randomly assigned to groups that received pregabalin 150 mg or placebo 1 h before surgery, with the dose repeated after 12 h. Assessments of pain and side effects were performed 48 h postoperatively. The incidences of chronic pain and hypoesthesia in the anterior chest were recorded 3 months after surgery. RESULTS: Ninety-four patients completed the study. Verbal numerical rating scale scores for pain and the need for additional analgesics were lower in the pregabalin group (n = 47) than the placebo group (n = 47) during 48 h postoperatively (P < 0.05). However, incidences of sedation and dizziness were higher in the pregabalin group (P < 0.05). There were no differences between the groups in the incidences of chronic pain and chest hypoesthesia at 3 months after surgery. CONCLUSIONS: Perioperative administration of pregabalin (150 mg twice per day) was effective in reducing early postoperative pain but not chronic pain in patients undergoing robot-assisted endoscopic thyroidectomy. Caution should be taken regarding dizziness and sedation.

Age-Related Difference in the Effect of Acute Hyperglycemia on Myocardial Ischemia-Reperfusion Injury.

Age and acute hyperglycemia are known risk factors of myocardial ischemia-reperfusion injury. We investigated age-related difference in the effect of acute hyperglycemia on myocardial ischemia-reperfusion injury in Sprague-Dawley rats (young, 3 months; middle-aged, 10-12 months; and old, 22-24 months). The rats received 1.2 g/kg dextrose or normal saline and were subjected to coronary artery occlusion for 45 minutes followed by reperfusion for 240 minutes. Infarct size and ejection fraction were measured. The levels of apoptosis-related proteins (C-PARP, Bcl-2, Bax, and cytochrome c) and autophagy-related proteins (Bnip3, Beclin-1, Atg5, and LC3B-II) were evaluated. Infarct size increased with acute hyperglycemia in young and middle-aged rats but not in old rats, whereas the reduction of ejection fraction after ischemia-reperfusion was aggravated by acute hyperglycemia in all age groups. Acute hyperglycemia increased Bnip3 and Beclin-1 expressions after ischemia-reperfusion in young and middle-aged rats but not in old rats, whereas it increased the expression of Bax, cytochrome c, Atg5, and LC3B-II only in young or middle-aged rats. Conclusively, acute hyperglycemia does not aggravate myocardial ischemia-reperfusion injury in old rats, unlike in young and middle-aged rats. This heterogeneity may be due to attenuated changes in protein signaling after ischemia-reperfusion injury under acute hyperglycemia in old rats.

Xenon preconditioning: the role of prosurvival signaling, mitochondrial permeability transition and bioenergetics in rats.

BACKGROUND: Similar to volatile anesthetics, the anesthetic noble gas xenon protects the heart from ischemia/reperfusion injury, but the mechanisms responsible for this phenomenon are not fully understood. We tested the hypothesis that xenon-induced cardioprotection is mediated by prosurvival signaling kinases that target mitochondria. METHODS: Male Wistar rats instrumented for hemodynamic measurements were subjected to a 30 min left anterior descending coronary artery occlusion and 2 h reperfusion. Rats were randomly assigned to receive 70% nitrogen/30% oxygen (control) or three 5-min cycles of 70% xenon/30% oxygen interspersed with the oxygen/nitrogen mixture administered for 5 min followed by a 15 min memory period. Myocardial infarct size was measured using triphenyltetrazolium staining. Additional hearts from control and xenon-pretreated rats were excised for Western blotting of Akt and glycogen synthase kinase 3 beta (GSK-3beta) phosphorylation and isolation of mitochondria. Mitochondrial oxygen consumption before and after hypoxia/reoxygenation and mitochondrial permeability transition pore opening were determined. RESULTS: Xenon significantly (P < 0.05) reduced myocardial infarct size compared with control (32 +/- 4 and 59% +/- 4% of the left ventricular area at risk; mean +/- sd) and enhanced phosphorylation of Akt and GSK-3beta. Xenon pretreatment preserved state 3 respiration of isolated mitochondria compared with the results obtained in the absence of the gas. The Ca(2+) concentration required to induce mitochondrial membrane depolarization was larger in the presence compared with the absence of xenon pretreatment (78 +/- 17 and 56 +/- 17 microM, respectively). The phosphoinositol-3-kinase-kinase inhibitor wortmannin blocked the effect of xenon on infarct size and respiration. CONCLUSIONS: These results indicate that xenon preconditioning reduces myocardial infarct size, phosphorylates Akt, and GSK-3beta, preserves mitochondrial function, and inhibits Ca(2+)-induced mitochondrial permeability transition pore opening. These data suggest that xenon-induced cardioprotection occurs because of activation of prosurvival signaling that targets mitochondria and renders them less vulnerable to ischemia-reperfusion injury.

The mechanism of helium-induced preconditioning: a direct role for nitric oxide in rabbits.

BACKGROUND: Helium produces preconditioning against myocardial infarction by activating prosurvival signaling, but whether nitric oxide (NO) generated by endothelial NO synthase plays a role in this phenomenon is unknown. We tested the hypothesis that NO mediates helium-induced cardioprotection in vivo. METHODS: Rabbits (n = 62) instrumented for hemodynamic measurement were subjected to a 30-min left anterior descending coronary artery occlusion and 3 h reperfusion, and received 0.9% saline (control) or three cycles of 70% helium-30% oxygen administered for 5 min interspersed with 5 min of an air-oxygen mixture before left anterior descending coronary artery occlusion in the absence or presence of pretreatment with the nonselective NOS inhibitor N-nitro-l-arginine methyl ester (L-NAME; 10 mg/kg), the selective inducible NOS inhibitor aminoguanidine hydrochloride (AG; 300 mg/kg), or selective neuronal NOS inhibitor 7-nitroindazole (7-NI; 50 mg/kg). In additional rabbits, the fluorescent probe 4,5-diaminofluroscein diacetate (DAF-2DA) and confocal laser microscopy were used to detect NO production in the absence or presence of helium with or without L-NAME pretreatment. RESULTS: Helium reduced (P < 0.05) infarct size (24% +/- 4% of the left ventricular area at risk; mean +/- sd) compared with control (46% +/- 3%). L-NAME, AG, and 7-NI did not alter myocardial infarct size when administered alone. L-NAME, but not 7-NI or AG, abolished helium-induced cardioprotection. Helium enhanced DAF-2DA fluorescence compared with control (26 +/- 8 vs 15 +/- 5 U, respectively). Pretreatment with L-NAME abolished these helium-induced increases in DAF-2DA fluorescence. CONCLUSIONS: The results indicate that cardioprotection by helium is mediated by NO that is probably generated by endothelial NOS in vivo.

Inhibition of glycogen synthase kinase or the apoptotic protein p53 lowers the threshold of helium cardioprotection in vivo: the role of mitochondrial permeability transition.

BACKGROUND: Prosurvival signaling kinases inhibit glycogen synthase kinase-3beta (GSK-3beta) activity and stimulate apoptotic protein p53 degradation. Helium produces cardioprotection by activating prosurvival kinases, but whether GSK and p53 inhibition mediate this process is unknown. We tested the hypothesis that inhibition of GSK or p53 lowers the threshold of helium cardioprotection via a mitochondrial permeability transition pore (mPTP)-dependent mechanism. METHODS: Rabbits (n = 85) instrumented for hemodynamic measurement and subjected to a 30 min left anterior descending coronary artery (LAD) occlusion and 3 h reperfusion received 0.9% saline (control), or 1, 3, or 5 cycles of 70% helium-30% oxygen administered for 5 min interspersed with 5 min of an air-oxygen mixture (fraction of inspired oxygen concentration = 0.30) before LAD occlusion. Other rabbits received the GSK inhibitor SB 216763 (SB21; 0.2 or 0.6 mg/kg), the p53 inhibitor pifithrin-alpha (PIF; 1.5 or 3.0 mg/kg), or SB21 (0.2 mg/kg) or PIF (1.5 mg/kg) plus helium (1 cycle) before LAD occlusion in the presence or absence of the mPTP opener atractyloside (5 mg/kg). RESULTS: Helium reduced (P < 0.05) myocardial infarct size (35 +/- 6 [n = 7], 25 +/- 4 [n = 7], and 20 +/- 3% [n = 6] of area at risk, 1, 3, and 5 cycles, respectively) compared with control (44 +/- 6% [n = 7]). SB21 (0.6 [n = 7] but not 0.2 mg/kg [n = 6]) and PIF (3.0 [n = 6] but not 1.5 mg/kg [n = 7]) also reduced necrosis. SB21 (0.2 mg/kg) or 1.5 mg/kg PIF (1.5 mg/kg) plus helium (1 cycle; n = 6 per group) decreased infarct size to an equivalent degree as three cycles of helium alone, and this cardioprotection was blocked by atractyloside (n = 7 per group). CONCLUSIONS: Inhibition of GSK or p53 lowers the threshold of helium-induced preconditioning via a mPTP-dependent mechanism in vivo.

Reactive oxygen species and mitochondrial adenosine triphosphate-regulated potassium channels mediate helium-induced preconditioning against myocardial infarction in vivo.

OBJECTIVES: Helium produces preconditioning by activating prosurvival kinases, but the roles of reactive oxygen species (ROS) or mitochondrial adenosine triphosphate-regulated potassium (K(ATP)) channels in this process are unknown. The authors tested the hypothesis that ROS and mitochondrial K(ATP) channels mediate helium-induced preconditioning in vivo. DESIGN: A randomized, prospective study. SETTING: A university research laboratory. PARTICIPANTS: Male New Zealand white rabbits. INTERVENTIONS: Rabbits (n = 64) were instrumented for the measurement of systemic hemodynamics and subjected to a 30-minute left anterior descending coronary artery (LAD) occlusion and 3 hours of reperfusion. In separate experimental groups, rabbits (n = 7 or 8 per group) were randomly assigned to receive 0.9% saline (control) or 3 cycles of 70% helium-30% oxygen administered for 5 minutes interspersed with 5 minutes of an air-oxygen mixture before LAD occlusion with or without the ROS scavengers N-acetylcysteine (NAC; 150 mg/kg) or N-2 mercaptoproprionyl glycine (2-MPG; 75 mg/kg), or the mitochondrial K(ATP) antagonist 5-hydroxydecanoate (5-HD; 5 mg/kg). Statistical analysis of data was performed with analysis of variance for repeated measures followed by Bonferroni's modification of a Student t test. MEASUREMENTS AND MAIN RESULTS: The myocardial infarct size was determined by using triphenyltetrazolium chloride staining and presented as a percentage of the left ventricular area at risk. Helium significantly (p < 0.05) reduced infarct size (23 +/- 4% of the area at risk; mean +/- standard deviation) compared with control (46 +/- 3%). NAC, 2-MPG, and 5-HD did not affect irreversible ischemic injury when administered alone (49 +/- 5%, 45 +/- 6%, and 45 +/- 3%), but these drugs blocked reductions in infarct size produced by helium (45 +/- 4%, 45 +/- 2%, and 44 +/- 3%). CONCLUSIONS: The results suggest that ROS and mitochondrial K(ATP) channels mediate helium-induced preconditioning in vivo.

Optimal conditions for Laryngeal Mask Airway insertion in children can be determined by the trapezius squeezing test.

STUDY OBJECTIVE: To evaluate the trapezius squeezing test as a criterion of adequate anesthetic depth for Laryngeal Mask Airway (LMA) insertion in children without neuromuscular blocking agents. DESIGN: Prospective, randomized clinical trial. SETTING: Operating room of a university hospital. PATIENTS: 45 ASA physical status I and II children, aged one to 6 years, undergoing minor surgical procedures. INTERVENTIONS: An LMA was inserted in each child after the trapezius squeezing test turned to be negative. MEASUREMENTS: Presence of coughing, gagging, gross purposeful movements, breath holding, laryngospasm, or desaturation during or within one minute of LMA insertion were recorded. Elapsed time of LMA insertion, end-tidal sevoflurane concentration, blood pressure, and heart rate values were also noted. MAIN RESULTS: LMA insertion was successful in 41 patients. Elapsed time to complete insertion was 5.7 +/- 1.9 minutes, and end-tidal sevoflurane concentration was 3.6 +/- 1.1 vol%. No marked hemodynamic changes occurred in any child. CONCLUSIONS: The trapezius squeezing test is a reliable clinical indicator to assess adequate anesthetic depth for LMA insertion in children without neuromuscular blocking agents.

Noble gases without anesthetic properties protect myocardium against infarction by activating prosurvival signaling kinases and inhibiting mitochondrial permeability transition in vivo.

BACKGROUND: The anesthetic noble gas, xenon, produces cardioprotection. We hypothesized that other noble gases without anesthetic properties [helium (He), neon (Ne), argon (Ar)] also produce cardioprotection, and further hypothesized that this beneficial effect is mediated by activation of prosurvival signaling kinases [including phosphatidylinositol-3-kinase, extracellular signal-regulated kinase, and 70-kDa ribosomal protein s6 kinase] and inhibition of mitochondrial permeability transition pore (mPTP) opening in vivo. METHODS: Rabbits (n = 98) instrumented for hemodynamic measurement and subjected to a 30-min left anterior descending coronary artery (LAD) occlusion and 3 h reperfusion received 0.9% saline (control), three cycles of 70% He-, Ne-, or Ar-30% O2 administered for 5 min interspersed with 5 min of 70% N2-30% O2 before LAD occlusion, or three cycles of brief (5 min) ischemia interspersed with 5 min reperfusion before prolonged LAD occlusion and reperfusion (ischemic preconditioning). Additional groups of rabbits received selective inhibitors of phosphatidylinositol-3-kinase (wortmannin; 0.6 mg/kg), extracellular signal-regulated kinase (PD 098059; 2 mg/kg), or 70-kDa ribosomal protein s6 kinase (rapamycin; 0.25 mg/kg) or mPTP opener atractyloside (5 mg/kg) in the absence or presence of He pretreatment. RESULTS: He, Ne, Ar, and ischemic preconditioning significantly (P < 0.05) reduced myocardial infarct size [23% +/- 4%, 20% +/- 3%, 22% +/- 2%, 17% +/- 3% of the left ventricular area at risk (mean +/- sd); triphenyltetrazolium chloride staining] versus control (45% +/- 5%). Wortmannin, PD 098059, rapamycin, and atractyloside alone did not affect infarct size, but these drugs abolished He-induced cardioprotection. CONCLUSIONS: The results indicate that noble gases without anesthetic properties produce cardioprotection by activating prosurvival signaling kinases and inhibiting mPTP opening in rabbits.

The efficacy of elastomeric patient-control module when connected to a balloon pump for postoperative epidural analgesia: A randomized, noninferiority trial.

When considering the principles of a pain control strategy by patients, reliable administration of additional bolus doses is important for providing the adequate analgesia and improving patient satisfaction. We compared the efficacy of elastomeric patient-control module (PCM) with conventional PCM providing epidural analgesia postoperatively.A noninferiority comparison was used. Eighty-six patients scheduled for open upper abdominal surgery were randomized to use either an elastomeric or conventional PCM connected to balloon pump. After successful epidural catheter insertion at T6-8 level, fentanyl (15-20 µg/kg) in 0.3% ropivacaine 100 mL was administered at basal rate 2 mL/h with bolus 2 mL and lock-out time 15 minutes. The primary outcome was the verbal numerical rating score for pain.The 95% confidence intervals for differences in pain scores during the first 48 hours postoperatively were <1, indicating noninferiority of the elastomeric PCM. The duration of pump reservoir exhaustion was shorter for the elastomeric PCM (mean [SD], 33 hours [8 hours] vs 40 hours [8 hours], P = 0.0003). There were no differences in the frequency of PCM use, additional analgesics, or adverse events between groups.The elastomeric PCM was as effective as conventional PCM with and exhibited a similar safety profile.

Effects of milrinone on blood flow of the Y-graft composed with the radial and the internal thoracic artery in patients with coronary artery disease.

OBJECTIVE: Milrinone has been known to dilate the internal thoracic artery (ITA) and the radial artery (RA). The effect of milrinone, however, on each graft is unclear when the left ITA (LITA) and the RA form a Y-graft. This study evaluated the changes in blood flow of a composite Y-graft in response to milrinone. METHODS: Thirty-two patients undergoing an isolated coronary artery bypass graft surgery were included in this study. A Y-graft was created with an in situ LITA and free RA graft attached to the proximal side of the LITA. Graft flow was measured by opening the graft end for 30s, and is expressed in 'ml/min'. Graft flow and hemodynamic data were recorded before and 10 min after intravenous milrinone (50 microg/kg) administration. RESULTS: Milrinone significantly increased the RA graft flow, measured while the LITA graft end was clamped, and total Y-graft flow. Respective graft flows were not increased by milrinone when both clamps were released simultaneously, in spite of a significant decrease in the resistance of both grafts. The ratio of flows through the RA and the LITA grafts was not changed by milrinone. CONCLUSION: Milrinone significantly reduced RA and LITA resistances and increased the total Y-graft flow. Milrinone might dilate each individual arterial graft to a different degree. Milrinone did not, however, change the flow ratio through the RA to LITA grafts when they were measured simultaneously. Therefore, it would not significantly divert graft flow to one side in a composite Y-graft.

The CobraPLA during anesthesia with controlled ventilation: a clinical trial of efficacy.

The CobraPLA (CPLA) is a relatively new supraglottic airway device that has not been sufficiently investigated. Here, we performed a prospective observational study to evaluate the efficacy of the CPLA during controlled ventilation. In 50 anesthetized and paralyzed patients undergoing elective surgery a CPLA was inserted and inflated to an intracuff pressure of 60 cm H2O. The success rate of insertion upon the first attempt was 82% (41/50), with a mean insertion time of 16.3 +/- 4.5 seconds. The adequacy of ventilation was assessed by observing the end tidal CO2 waveform, movement of the chest wall, peak airway pressure (13.5 cm H2O), and leak fraction (4%). We documented the airway sealing pressure (22.5 cm H2O) and noted that the the site of gas leaks at that pressure were either at the neck (52%), the abdomen (46%), or both (2%). In 44 (88%) patients, the vocal cords were visible in the fiberoptic view through the CPLA. There was no gastric insufflation during the anesthesia. Respiratory and hemodynamic parameters remained stable during CPLA insertion. Postoperative blood staining of CPLA was minimal, occurring in 22% (11/50) of patients. Mild and moderate throat soreness was reported in 44% (22/50) and 4% (2/50) of patients, respectively. Lastly, mild dysphonia was observed in 6% (3/50) of patients and mild dysphagia in 10% (5/50) of patients. Our results indicated that the CPLA is both easy to place and allows adequate ventilation during controlled ventilation.

Effect of a Single Bolus of Erythropoietin on Renoprotection in Patients Undergoing Thoracic Aortic Surgery With Moderate Hypothermic Circulatory Arrest.

BACKGROUND: Acute kidney injury (AKI) is associated with high morbidity and mortality. Recombinant human erythropoietin has been shown to exert cytoprotection against ischemia. This study examined the effect of erythropoietin in preventing AKI during thoracic aortic surgery with moderate hypothermic circulatory arrest. METHODS: In this double-blind, randomized study, 66 patients undergoing thoracic aortic surgery with moderate hypothermic circulatory arrest (target temperature, 28°C) randomly received either erythropoietin 500 IU·kg(-1) or the same amount of normal saline intravenously after anesthesia induction. The primary endpoint was incidence of AKI defined according to the RIFLE criteria during the first 7 postoperative days. RESULTS: AKI occurred in 60% of all patients. The two groups did not show any differences in the incidence and severity of AKI. Also, there was no difference in the level of serum neutrophil gelatinase-associated lipocalin between the groups. The cardiac index was higher in the erythropoietin group, however, immediately after weaning from cardiopulmonary bypass (p = 0.02). Furthermore, postoperative cardiac complications and prolonged vasopressor dependence were reduced in the erythropoietin group (p = 0.04 and p = 0.049, respectively). CONCLUSIONS: A single bolus administration of erythropoietin 500 IU·kg(-1) at anesthesia induction failed to provide renoprotection in patients who underwent thoracic aortic surgery with moderate hypothermic circulatory arrest. However, erythropoietin significantly reduced cardiac complications, and lowered the incidence of prolonged vasopressor dependence.

Thrombus entrapped by patent foramen ovale in a patient with pulmonary embolism: a case report.

Thrombus-in-transit appears to increase the risk of mortality compared to pulmonary embolism alone and can require alteration in therapeutic plan. We present the case of a biatrial thromboembolus caught in transit across a patent foramen ovale diagnosed by intraoperative transesophageal echocardiogram in a 69-year-old female with acute pulmonary embolism and subsequent acute cerebral infarction. We suggest that echocardiography should be performed in a patient with suspected pulmonary thromboembolism to evaluate right heart function and diagnose emboli in transit.