Associations among preoperative transthoracic echocardiography variables and cerebral near-infrared spectroscopy values at baseline before anesthesia in patients undergoing cardiac surgery: a retrospective observational study.

Cerebral tissue oximetry with near-infrared spectroscopy (NIRS) is used to monitor cerebral oxygenation during cardiac surgery. To date, reduced baseline cerebral NIRS values have been attributed to reduced cerebral blood flow primarily based on a significant positive correlation between left ventricular ejection fraction (LVEF) and baseline rSO2 measured with the INVOS 5100C oximeter. Reportedly, however, rSO2, but not StO2 measured with the FORESIGHT Elite oximeter, correlated with LVEF. We, thus, investigated associations among baseline NIRS values measured with three different oximeters before anesthesia for cardiac surgery and preoperative transthoracic echocardiography (TTE) variables, including LVEF, to examine whether there are inter-device differences in associations among baseline NIRS values and TTE variables. Using Spearman's correlation coefficient, we retrospectively investigated associations among 15 preoperative TTE variables, including LVEF, and baseline NIRS values, including rSO2, StO2, and TOI with the NIRO-200NX oximeter in 1346, 515, and 301 patients, respectively. Only rSO2 (p < 0.00001), but not TOI or StO2 (p > 0.05), positively correlated with LVEF. On the other hand, baseline rSO2, TOI, and StO2 consistently, negatively correlated with the left atrial diameter index (LADI), early diastolic transmitral flow velocity (E), E-to-early diastolic mitral annular velocity ratio (E/e'), estimated right ventricular systolic pressure (eRVP), and inferior vena cava diameter index (IVCDI) (p < 0.0005 to p < 0.00001). Because all of these five TTE variables could be positively associated with right as well as left ventricular filling pressure, our results indicated that reduced baseline NIRS values were consistently associated not with reduced LVEF but with TTE findings indicative of elevated biventricular filling pressure. Our data suggest that regional venous congestion greatly contributes to reduced baseline NIRS values in patients undergoing cardiac surgery.

Distinct Profiles of Desensitization of µ-Opioid Receptors Caused by Remifentanil or Fentanyl: In Vitro Assay with Cells and Three-Dimensional Structural Analyses.

Remifentanil (REM) and fentanyl (FEN) are commonly used analgesics that act by activating a µ-opioid receptor (MOR). Although optimal concentrations of REM can be easily maintained during surgery, it is sometimes switched to FEN for optimal pain regulation. However, standards for this switching protocol remain unclear. Opioid anesthetic efficacy is decided in part by MOR desensitization; thus, in this study, we investigated the desensitization profiles of REM and FEN to MOR. The efficacy and potency during the 1st administration of REM or FEN in activating the MOR were almost equal. Similarly, in ß arrestin recruitment, which determines desensitization processes, they showed no significant differences. In contrast, the 2nd administration of FEN resulted in a stronger MOR desensitization potency than that of REM, whereas REM showed a higher internalization potency than FEN. These results suggest that different ß arrestin-mediated signaling caused by FEN or REM led to their distinct desensitization and internalization processes. Our three-dimensional analysis, with in silico binding of REM and FEN to MOR models, highlighted that REM and FEN bound to similar but distinct sites of MOR and led to distinct ß arrestin-mediated profiles, suggesting that distinct binding profiles to MOR may alter ß arrestin activity, which accounts for MOR desensitization and internalization.

Genome-Wide Association Study Identifies Genetic Polymorphisms Associated with Estimated Minimum Effective Concentration of Fentanyl in Patients Undergoing Laparoscopic-Assisted Colectomy.

Sensitivity to opioids varies widely among individuals. To identify potential candidate single-nucleotide polymorphisms (SNPs) that may significantly contribute to individual differences in the minimum effective concentration (MEC) of an opioid, fentanyl, we conducted a three-stage genome-wide association study (GWAS) using whole-genome genotyping arrays in 350 patients who underwent laparoscopic-assisted colectomy. To estimate the MEC of fentanyl, plasma and effect-site concentrations of fentanyl over the 24 h postoperative period were estimated with a pharmacokinetic simulation model based on initial bolus doses and subsequent patient-controlled analgesia doses of fentanyl. Plasma and effect-site MECs of fentanyl were indicated by fentanyl concentrations, estimated immediately before each patient-controlled analgesia dose. The GWAS revealed that an intergenic SNP, rs966775, that mapped to 5p13 had significant associations with the plasma MEC averaged over the 6 h postoperative period and the effect-site MEC averaged over the 12 h postoperative period. The minor G allele of rs966775 was associated with increases in these MECs of fentanyl. The nearest protein-coding gene around this SNP was DRD1, encoding the dopamine D1 receptor. In the gene-based analysis, the association was significant for the SERP2 gene in the dominant model. Our findings provide valuable information for personalized pain treatment after laparoscopic-assisted colectomy.

Rs11726196 Single-Nucleotide Polymorphism of the Transient Receptor Potential Canonical 3 (TRPC3) Gene Is Associated with Chronic Pain.

Chronic pain is reportedly associated with the transient receptor potential canonical 3 (TRPC3) gene. The present study examined the genetic associations between the single-nucleotide polymorphisms (SNPs) of the TRPC3 gene and chronic pain. The genomic samples from 194 patients underwent linkage disequilibrium (LD) analyses of 29 SNPs within and around the vicinity of the TRPC3 gene. We examined the associations between the SNPs and the susceptibility to chronic pain by comparing the genotype distribution of 194 patients with 282 control subjects. All SNP genotype data were extracted from our previous whole-genome genotyping results. Twenty-nine SNPs were extracted, and a total of four LD blocks with 15 tag SNPs were observed within and around the TRPC3 gene. We further analyzed the associations between these tag SNPs and chronic pain. The rs11726196 SNP genotype distribution of patients was significantly different from the control subjects even after multiple-testing correction with the number of SNPs. The TT + TG genotype of rs11726196 is often carried by chronic pain patients, suggesting a causal role for the T allele. These results contribute to our understanding of the genetic risk factors for chronic pain.

Single-Nucleotide Polymorphisms of the PAR2 and IL-17A Genes Are Significantly Associated with Chronic Pain.

Patients with chronic pain are affected psychologically and socially. There are also individual differences in treatment efficacy. Insufficient research has been conducted on genetic polymorphisms that are related to individual differences in the susceptibility to chronic pain. Autoimmune disorders can lead to inflammation and chronic pain; therefore, we focused on the autoimmune-related protease-activated receptor 2 (PAR2/F2RL1) and interleukin 17A (IL-17A/IL17A) genes. PAR2 and IL-17A are associated with autoimmune diseases that lead to chronic pain, and PAR2 regulates T-helper (Th) cell activation and differentiation. We hypothesized that the PAR2 and IL-17A genes are associated with chronic pain. The present study used a case-control design to statistically examine associations between genetic polymorphisms and the vulnerability to chronic pain. The rs2243057 polymorphism of the PAR2 gene and rs3819025 polymorphism of the IL-17A gene were previously reported to be associated with pain- or autoimmune-related phenotypes. Thus, these polymorphisms were investigated in the present study. We found that both rs2243057 and rs3819025 were significantly associated with a susceptibility to chronic pain. The present findings revealed autoimmune-related genetic factors that are involved in individual differences in chronic pain, further aiding understanding of the pathomechanism that underlies chronic pain and possibly contributing to future personalized medicine.

Implementation of an electronic identification system in the setting of perioperative autologous cell salvage transfusion: Experience at a university hospital.

Perioperative autologous cell salvage (PACS) is one of the effective strategies in patient blood management (PBM). However, mistransfusion, in which the wrong blood is transfused to the wrong patient, of PACS units has been reported. In this study, we implemented a bar code-based electronic identification system (EIS) for blood transfusion in the setting of PACS transfusion. Between February 2009 and December 2020, a total of 12341 surgical patients (9% of whom received surgical interventions) received blood transfusion, among whom 6595 (54 %) received autologous blood transfusion alone, 2877 (23 %) both autologous and allogeneic blood transfusions, and 2869 (23 %) allogeneic blood transfusion alone. Among autologous blood conservation techniques, PACS units were transfused to 7873 patients (83 %) without a single mistransfusion. Rates of overall compliance with the electronic pre-transfusion check at the bedside for all autologous units and PACS units were 98.8 and 98.5 %, respectively. Our observations suggest that a bar code-based EIS can be successfully applied to PACS transfusion, as well as allogeneic blood transfusion in operating rooms.

Novel Opioid Analgesics for the Development of Transdermal Opioid Patches That Possess Morphine-Like Pharmacological Profiles Rather Than Fentanyl: Possible Opioid Switching Alternatives Among Patch Formula.

BACKGROUND: Transdermal fentanyl is widely used in the treatment of severe pain because of convenience, safety, and stable blood concentrations. Nevertheless, patients often develop tolerance to fentanyl, necessitating the use of other opioids; transdermal buprenorphine patch is widely used as an analgesic agent, though available formulation does not provide comparable analgesic effect as transdermal fentanyl patch. Opioids bind to the opioid receptor (OR) to activate both G protein-mediated and ß-arrestin-mediated pathways. We synthesized morphine-related compounds with high transdermal absorbability (N1 and N2) and evaluated their OR activities pharmacologically in comparison with fentanyl and morphine. METHODS: In cells stably expressing µ-opioid receptor (MOR), δ-opioid receptor (DOR), and κ-opioid receptor (KOR), G protein-mediated pathways were assessed using the CellKey and an intracellular cyclic adenosine monophosphate (cAMP) assay, while ß-arrestin-mediated pathways were analyzed with ß-arrestin recruitment and receptor internalization assays. Furthermore, analgesic effects were evaluated using a tail-flick test in mice, and the analgesic effect on fentanyl-tolerant mice was evaluated. RESULTS: In the CellKey and cAMP assays, both N1 and N2 showed the highest affinity for MOR and acted as full agonists as well as partial agonists for DOR and KOR. In the ß-arrestin and internalization assays, only fentanyl acted as a full agonist; N1 and N2 acted as partial agonists of MOR. In the mouse tail-flick test, N1 and N2 showed analgesic effects equivalent to those of fentanyl and morphine. In fentanyl-tolerant mice, fentanyl showed a diminished analgesic effect, whereas N1 and N2 as well as morphine retained their analgesic effects. CONCLUSIONS: While N1 and N2 have higher transdermal absorbability than fentanyl, they also have analgesic effects comparable to those of morphine, suggesting that they may be attractive compounds for the development of novel opioid patches for transitioning from fentanyl patches.

Anti-Inflammatory Action of Dexmedetomidine on Human Microglial Cells.

Neuroinflammation, where inflammatory cytokines are produced in excess, contributes to the pathogenesis of delirium. Microglial cells play a central role in neuroinflammation by producing and releasing inflammatory cytokines in response to infection, tissue damage and neurodegeneration. Dexmedetomidine (DEX) is a sedative, which reduces the incidence of delirium. Thus, we hypothesized that DEX may alleviate delirium by exhibiting anti-inflammatory action on microglia. In the present study, we investigated the anti-inflammatory action of DEX on human microglial HMC3 cells. The results indicated that DEX partially suppressed the IL-6 and IL-8 production by lipopolysaccharide (LPS)-stimulated HMC3 cells as well as the phosphorylation of p38 MAPK and IκB and the translocation of NF-κB. Furthermore, DEX substantially suppressed IL-6 and IL-8 production by unstimulated HMC3 cells as wells as the phosphorylation of p38 MAPK and IκB and the translocation of NF-κB. These observations suggest that DEX exhibits anti-inflammatory action on not only LPS-stimulated but also unstimulated microglial cells via the suppression of inflammatory signaling and cytokine production.

Evaluation of the Intracellular Signaling Activities of κ-Opioid Receptor Agonists, Nalfurafine Analogs; Focusing on the Selectivity of G-Protein- and ß-Arrestin-Mediated Pathways.

Opioid receptors (ORs) are classified into three types (µ, δ, and κ), and opioid analgesics are mainly mediated by µOR activation; however, their use is sometimes restricted by unfavorable effects. The selective κOR agonist nalfurafine was initially developed as an analgesic, but its indication was changed because of the narrow safety margin. The activation of ORs mainly induces two intracellular signaling pathways: a G-protein-mediated pathway and a ß-arrestin-mediated pathway. Recently, the expectations for κOR analgesics that selectively activate these pathways have increased; however, the structural properties required for the selectivity of nalfurafine are still unknown. Therefore, we evaluated the partial structures of nalfurafine that are necessary for the selectivity of these two pathways. We assayed the properties of nalfurafine and six nalfurafine analogs (SYKs) using cells stably expressing κORs. The SYKs activated κORs in a concentration-dependent manner with higher EC50 values than nalfurafine. Upon bias factor assessment, only SYK-309 (possessing the 3S-hydroxy group) showed higher selectivity of G-protein-mediated signaling activities than nalfurafine, suggesting the direction of the 3S-hydroxy group may affect the ß-arrestin-mediated pathway. In conclusion, nalfurafine analogs having a 3S-hydroxy group, such as SYK-309, could be considered G-protein-biased κOR agonists.

Paths of thoracic epidural catheters in children undergoing the Nuss procedure for pectus excavatum repair.

PURPOSE: To investigate the paths of thoracic epidural catheters in children, this retrospective study was performed. METHODS: We investigated 73 children aged 4 to 12 (mean ± SD 7.8 ± 2.3) years, who underwent the Nuss procedure for pectus excavatum repair under combined general and epidural anesthesia over a 5-year period at Tokyo Metropolitan Police Hospital. Following induction of general anesthesia, we inserted a radiopaque epidural catheter via the T5/6 or T6/7 interspace and advanced for 5 cm cephalad in the thoracic epidural space. We evaluated the paths of the epidural catheters on plain chest radiographs after surgery. RESULTS: The median level for the catheter tip location was T3 (range C6-T7), while the median number of vertebrae crossed by the catheter tips was 2.5. In most children, the catheters advanced straight for the first 2-3 cm (1-1.5 vertebrae) in the thoracic epidural space. However, they continued to advance straight in only 25 children, while they exhibited curved or coiled paths in the remaining 48. The catheter tips were located at higher levels in children with straight epidural catheter paths [median (range) T2 (C6-T4)] than in those with curved or coiled paths after the initial 2-3 cm [median (range) T4 (T2-T7)] (p < 0.0001). CONCLUSIONS: Our findings indicate that the course of epidural catheters in children is unpredictable after the first 2-3 cm in the thoracic epidural space. Clinicians should be aware of such findings, although further studies are required for confirmation.

Continuing versus withholding angiotensin receptor blocker (ARB)/calcium channel blocker (CCB) combination tablets during perioperative periods in patients undergoing minor surgery: a single-blinded randomized controlled trial.

PURPOSE: This trial was conducted to compare effects of continuing versus withholding single-pill combination tablets consisting of angiotensin receptor blockers (ARBs) and calcium channel blockers (CCBs) on perioperative hemodynamics and clinical outcomes. METHODS: Patients undergoing minor abdominal or urological surgery (n = 106) were randomly assigned to Group C, in which ARB/CCB combination tablets were continued until surgery, or Group W, in which they were withheld within 24 h of surgery. Perioperative hemodynamics and clinical outcomes were compared between the Groups. RESULTS: The incidence of hypotension during anesthesia requiring repeated treatment with vasoconstrictors was higher in Group C than Group W (p = 0.0052). Blood pressure during anesthesia was generally lower in Group C than Group W (p < 0.05) despite significantly more doses of ephedrine and phenylephrine administrated in Group C (p = 0.0246 and p = 0.0327, respectively). The incidence of postoperative hypertension did not differ between Groups (p = 0.3793). Estimated glomerular filtration rate (eGFR) on the preoperative day did not differ between Groups (p = 0.7045), while eGFR was slightly lower in Group C than Group W on the first and third postoperative days (p = 0.0400 and p = 0.0088, respectively), although clinically relevant acute kidney injury did not develop. CONCLUSIONS: Continuing ARB/CCB combination tablets preoperatively in patients undergoing minor surgery increased the incidence of hypotension during anesthesia, increased requirements of vasoconstrictors to treat hypotension, and might deteriorate postoperative renal function, albeit slightly. These results suggest that withholding ARB/CCB tablets preoperatively is preferable to continuing them. CLINICAL TRIAL REGISTRATION: This trial is registered with the Japan Registry of Clinical Trials (jRCT) at Japanese Ministry of Health, Labour, and Welfare (Trial ID: jRCT1031190027).

Effects of the Multidisciplinary Preoperative Clinic on the Incidence of Elective Surgery Cancellation.

To evaluate effects of the multidisciplinary preoperative clinic (POC) consisting of anesthesiologists, dentists, pharmacists, and nurses on elective surgery cancellation, we retrospectively investigated patients who underwent elective non-cardiac, non-obstetric surgeries between October, 2018 and March, 2019 (before the POC establishment: Group 1) and between October, 2019 and March, 2020 (after the POC establishment: Group 2). Among reasons for surgery cancellation allocated into eight categories, three reasons for cancellation (related to consent authorization, medication, and significant comorbidities) were considered preventable. We compared incidences of overall and preventable cancellations of surgeries between 4,198 patients in Group 1 and 4,664 patients in Group 2, who had significantly different clinical backgrounds, including the ASA-PS class. There was no significant difference in the incidence of overall cancellation between Group 1 and Group 2 (4.1% vs. 4.1%, p = 0.96). However, the incidence of preventable cancellation was significantly lower in Group 2 than in Group 1 (0.4% vs. 0.7%, p = 0.045). In addition, the incidence of overall cancellation was significantly lower in 3,741 Group 2 patients visiting the POC than in 5,121 patients not visiting the POC in both Groups (3.2% vs. 4.7%, p < 0.001). Further, in 3,423 pairs of patients with comparable clinical backgrounds created from both Groups using propensity score matching, incidences of overall cancellation (2.2% vs. 3.1%) and preventable cancellation (0.1% vs. 0.6%) were significantly lower in Group 2 than in Group 1 (p = 0.036 and 0.008, respectively). In conclusion, the multidisciplinary POC was effective in reducing elective surgery cancellation.

Heparan sulfate 3-O-sulfotransferase 4 is genetically associated with herpes zoster and enhances varicella-zoster virus-mediated fusogenic activity.

Acute pain that is associated with herpes zoster (HZ) can become long-lasting neuropathic pain, known as chronic post-herpetic neuralgia (PHN), especially in the elderly. HZ is caused by the reactivation of latent varicella-zoster virus (VZV), whereas PHN is not attributed to ongoing viral replication. Although VZV infection reportedly induces neuronal cell fusion in humans, the pathogenesis of PHN is not fully understood. A genome-wide association study (GWAS) revealed significant associations between PHN and the rs12596324 single-nucleotide polymorphism (SNP) of the heparan sulfate 3-O-sulfotransferase 4 (HS3ST4) gene in a previous study. To further examine whether this SNP is associated with both PHN and VZV reactivation, associations between rs12596324 and a history of HZ were statistically analyzed using GWAS data. HZ was significantly associated with the rs12596324 SNP of HS3ST4, indicating that HS3ST4 is related to viral replication. We investigated the influence of HS3ST4 expression on VZV infection in cultured cells. Fusogenic activity after VZV infection was enhanced in cells with HS3ST4 expression by microscopy. To quantitatively evaluate the fusogenic activity, we applied cytotoxicity assay and revealed that HS3ST4 expression enhanced cytotoxicity after VZV infection. Expression of the VZV glycoproteins gB, gH, and gL significantly increased cytotoxicity in cells with HS3ST4 expression by cytotoxicity assay, consistent with the fusogenic activity as visualized by fluorescence microscopy. HS3ST4 had little influence on viral genome replication, revealed by quantitative real-time polymerase chain reaction. These results suggest that HS3ST4 enhances cytotoxicity including fusogenic activity in the presence of VZV glycoproteins without enhancing viral genome replication.

Genome-wide association study identifies candidate loci associated with chronic pain and postherpetic neuralgia.

BACKGROUND: Human twin studies and other studies have indicated that chronic pain has heritability that ranges from 30% to 70%. We aimed to identify potential genetic variants that contribute to the susceptibility to chronic pain and efficacy of administered drugs. We conducted genome-wide association studies (GWASs) using whole-genome genotyping arrays with more than 700,000 markers in 191 chronic pain patients and a subgroup of 89 patients with postherpetic neuralgia (PHN) in addition to 282 healthy control subjects in several genetic models, followed by additional gene-based and gene-set analyses of the same phenotypes. We also performed a GWAS for the efficacy of drugs for the treatment of pain. RESULTS: Although none of the single-nucleotide polymorphisms (SNPs) were found to be genome-wide significantly associated with chronic pain (p ≥ 1.858 × 10-7), the GWAS of PHN patients revealed that the rs4773840 SNP within the ABCC4 gene region was significantly associated with PHN in the trend model (nominal p = 1.638 × 10-7). In the additional gene-based analysis, one gene, PRKCQ, was significantly associated with chronic pain in the trend model (adjusted p = 0.03722). In the gene-set analysis, several gene sets were significantly associated with chronic pain and PHN. No SNPs were significantly associated with the efficacy of any of types of drugs in any of the genetic models. CONCLUSIONS: These results suggest that the PRKCQ gene and rs4773840 SNP within the ABCC4 gene region may be related to the susceptibility to chronic pain conditions and PHN, respectively.

Cerebral oxygen saturation (rSO2) during cardiopulmonary bypass (CPB) measured using the INVOS oximeter closely correlates with baseline rSO2.

Baseline cerebral regional saturation (rSO2) measured using the INVOS 5100C (Medtronic, MN, USA) varies widely among patients with cardiac and/or renal diseases. To identify significant correlates of baseline rSO2 and to investigate intraoperative rSO2 changes, we conducted a retrospective study in 494 patients undergoing on-pump cardiovascular surgery. Correlations between preoperative blood laboratory test variables and baseline rSO2 before anesthesia were examined. Intraoperative rSO2 changes were analyzed. Of all the variables examined, log-transformed B-type natriuretic peptide (BNP) most significantly and negatively correlated with baseline rSO2 (r = - 0.652, p < 0.0001). Intraoperatively, rSO2 showed the lowest value during cardiopulmonary bypass (CPB) (median rSO2: 56.2% during CPB vs. 63.9% at baseline, p < 0.0001). Although rSO2 during CPB correlated positively with hemoglobin concentration and oxygen delivery during CPB (r = 0.192, p < 0.0001; and r = 0.172, p = 0.0001, respectively), it correlated much more closely with baseline rSO2 (r = - 0.589, p < 0.0001). Thus, patients showing low baseline rSO2 primarily associated with preoperatively high BNP continued to show low rSO2 even during CPB independent of hemodynamics artificially controlled by CPB. Our findings suggest that low baseline rSO2 in patients with high BNP due to cardiac and/or renal diseases is more likely to result from tissue edema causing alterations in optical pathlength and thus in calculated rSO2 values, not readily modifiable with CPB, rather than actual cerebral hemodynamic alterations readily modifiable with CPB. These may partly explain why the INVOS oximeter is a trend monitor requiring baseline measures.

In Vitro Analyses of Spinach-Derived Opioid Peptides, Rubiscolins: Receptor Selectivity and Intracellular Activities through G Protein- and ß-Arrestin-Mediated Pathways.

Activated opioid receptors transmit internal signals through two major pathways: the G-protein-mediated pathway, which exerts analgesia, and the ß-arrestin-mediated pathway, which leads to unfavorable side effects. Hence, G-protein-biased opioid agonists are preferable as opioid analgesics. Rubiscolins, the spinach-derived naturally occurring opioid peptides, are selective δ opioid receptor agonists, and their p.o. administration exhibits antinociceptive effects. Although the potency and effect of rubiscolins as G-protein-biased molecules are partially confirmed, their in vitro profiles remain unclear. We, therefore, evaluated the properties of rubiscolins, in detail, through several analyses, including the CellKeyTM assay, cADDis® cAMP assay, and PathHunter® ß-arrestin recruitment assay, using cells stably expressing µ, δ, κ, or µ/δ heteromer opioid receptors. In the CellKeyTM assay, rubiscolins showed selective agonistic effects for δ opioid receptor and little agonistic or antagonistic effects for µ and κ opioid receptors. Furthermore, rubiscolins were found to be G-protein-biased δ opioid receptor agonists based on the results obtained in cADDis® cAMP and PathHunter® ß-arrestin recruitment assays. Finally, we found, for the first time, that they are also partially agonistic for the µ/δ dimers. In conclusion, rubiscolins could serve as attractive seeds, as δ opioid receptor-specific agonists, for the development of novel opioid analgesics with reduced side effects.

Unique strategy using a standard double lumen tube during one lung ventilation for successful intraoperative airway management in patients with a giant bulla on the ventilated side: case series.

Giant lung bullae are usually seen in patients with severe chronic obstructive pulmonary disease. Over time, air trapping leads to severe dyspnea and CO2 accumulation. In severe cases, overinflation and rupture of the bulla can cause secondary life-threatening tension pneumothorax. Since positive pressure ventilation exerts deleterious effects on the bulla, general anesthesia is always challenging in patients with giant bullae. We encountered remarkable intraoperative hypercapnia and decreased tidal volume in a 58-year-old male patient with bilateral bullae who underwent right upper bullectomy, due to overinflation of a bulla located in the upper lobe of the ventilated side. Through this experience, to avoid further overinflation, we devised an original, unique and simple airway management strategy using a standard double lumen tube (DLT), which only requires slightly deeper advancement of the DLT to achieve selective lobar blockade during one lung ventilation (OLV). Following the first case, we used this strategy in a 48-year-old male patient who underwent left giant bullectomy, resulting in successful airway management without overinflation during OLV. We recommend our strategy as an option for successful intraoperative airway management during OLV in select bullectomy patients with bilateral giant bullae.

B-Type Natriuretic Peptide and Hemoglobin are Two Major Factors Significantly Associated With Baseline Cerebral Oxygen Saturation Measured Using the INVOS Oximeter in Patients Undergoing Off-Pump Coronary Artery Bypass Graft Surgery.

OBJECTIVES: To investigate an association between the preoperative plasma B-type natriuretic peptide (BNP) concentration and cerebral regional saturation (rSO2) measured using the INVOS oximeter (Medtronic, Minneapolis, MN). DESIGN: A retrospective data analysis. SETTING: Single university hospital. PARTICIPANTS: Patients undergoing off-pump coronary artery bypass (OPCAB) surgery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Associations of variables obtained from preoperative blood laboratory tests and transthoracic echocardiography with baseline rSO2 before induction of general anesthesia were investigated using bivariate and multivariate regression analyses in 330 OPCAB patients. With bivariate analyses, age; body size-related variables such as weight and body surface area; hematologic function-related variables such as blood hemoglobin (Hb) concentration and arterial oxygen saturation; renal function-related variables including estimated glomerular filtration rate, creatinine, and blood urea nitrogen; hepatic function-related variables including cholinesterase, albumin, total bilirubin, and alanine aminotransferase; serum electrolytes including sodium, chloride, and phosphorus; BNP or log-transformed BNP; and 13 transthoracic echocardiography variables such as left ventricular ejection fraction highly significantly correlated with baseline rSO2 (p < 0.0001). However, the multiple regression analysis revealed that only BNP and Hb remained major factors significantly associated with baseline rSO2 (p < 0.0001), while estimated glomerular filtration rate, arterial oxygen saturation, and body surface area remained minor factors (p < 0.05). Baseline rSO2 correlated better with log-transformed BNP than with BNP, indicating that rSO2 correlated with BNP in an exponential fashion. CONCLUSIONS: Preoperative BNP and Hb concentrations were 2 major factors associated with INVOS rSO2 in patients undergoing OPCAB.

Anesthetic Management of Patients Undergoing Right Lung Surgery After Left Upper Lobectomy: Selection of Tubes for One-Lung Ventilation (OLV) and Oxygenation During OLV.

OBJECTIVE: To investigate anesthesia management in patients undergoing right lung surgery after a previous left upper lobectomy (LUL) that may require special precautions since angulation of the left bronchus can hamper correct placement of a left-sided double-lumen tube (DLT), and one-lung ventilation (OLV) depending solely on the left lower lobe may lead to inadequate oxygenation. DESIGN: A retrospective data analysis. SETTING: Single university hospital. PARTICIPANTS: Patients underwent right lung surgery after previous LUL. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Anesthesia management was investigated in 18 patients who underwent right lung surgery following LUL. All intubation procedures were performed under bronchoscopic guidance to prevent airway trauma. OLV could be achieved with a left-sided DLT in 12 patients, while tubes other than this were required in 6 patients, including a right-sided DLT (n = 3) and a bronchial blocker (n = 3). The presence or absence of remarkable bronchial angulation, characterized by a combination of a wide (>140°) angle between the trachea and left main bronchus and a narrow (<100°) angle between the left main and lower bronchi critically affected tube selections. The minimum SpO2 during OLV was 90.9±4.1%. In 2 patients, intermittent bilateral ventilation was required to treat desaturation. In all the patients, the scheduled surgery could be completed. CONCLUSIONS: Extent of left bronchial angulations had a critical impact on whether or not a left-sided DLT could be used in patients undergoing right lung surgery after LUL.

Effects of dexmedetomidine on hemodynamics and respiration in intubated, spontaneously breathing patients after endoscopic submucosal dissection for cervical esophageal or pharyngeal cancer.

PURPOSE: We evaluated the hemodynamic and respiratory effects of dexmedetomidine in intubated, spontaneously breathing patients after endoscopic submucosal dissection (ESD) for cervical esophageal or pharyngeal cancer. METHODS: This retrospective study included 129 patients aged 66.5 ± 8.3 years, who underwent ESD under general anesthesia, and who were kept intubated overnight to prevent airway obstruction, receiving sedation with dexmedetomidine. Constant dexmedetomidine infusion at 0.51 ± 0.16 µg/kg/h was started intraoperatively (n = 109) or postoperatively (n = 20), following (n = 29) or not following (n = 100) loading doses, and continued until extubation. Hemodynamic and respiratory variables, and Richmond Agitation-Sedation Scale (RASS) score, were recorded. RESULTS: Postoperatively, 129 patients remained intubated while breathing spontaneously for 16.4 ± 3.3 h, and 124 patients could be sedated solely with dexmedetomidine, whereas 5 required rescue sedatives. During infusion, blood pressure decreased progressively until 12 h, whereas heart rate decreased only at 3 h. Hemodynamic alterations during dexmedetomidine infusion greatly depended not only on its hemodynamic effects but also on baseline hemodynamics before anesthesia. No serious adverse effect was noted. CONCLUSION: Dexmedetomidine in intubated, spontaneously breathing patients after ESD was safe and effective. Patient baseline hemodynamics could significantly affect hemodynamics during drug infusion. Without loading doses, plasma drug concentrations were expected to increase progressively. A progressive decrease in blood pressure and unchanged heart rate after an initial decrease suggested that hemodynamic effects of dexmedetomidine in our patients might differ from those reported in young volunteers, although further studies are required to elucidate these points.