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Thompson, N. R.; Fan, Y.; Dalton, J. E.; Jehi, L.; Rosenbaum, B. P.; Vadera, S.; Griffith, S. D.
Med Care. 2015: pp. 374-9.
ABSTRACT: BACKGROUND: Recently, van Walraven developed a weighted summary score (VW) based on the 30 comorbidities from the Elixhauser comorbidity system. One of the 30 comorbidities, cardiac arrhythmia, is currently excluded as a comorbidity indicator in administrative datasets such as the Nationwide Inpatient Sample (NIS), prompting us to examine the validity of the VW score and its use in the NIS. METHODS: Using data from the 2009 Maryland State Inpatient Database, we derived weighted summary scores to predict in-hospital mortality based on the full (30) and reduced (29) set of comorbidities and compared model performance of these and other comorbidity summaries in 2009 NIS data. RESULTS: Weights of our derived scores were not sensitive to the exclusion of cardiac arrhythmia. When applied to NIS data, models containing derived summary scores performed nearly identically (c statistics for 30 and 29 variable-derived summary scores: 0.804 and 0.802, respectively) to the model using all 29 comorbidity indicators (c=0.809), and slightly better than the VW score (c=0.793). Each of these models performed substantially better than those based on a simple count of Elixhauser comorbidities (c=0.745) or a categorized count (0, 1, 2, or >/= 3 comorbidities; c=0.737). CONCLUSIONS: The VW score and our derived scores are valid in the NIS and are statistically superior to summaries using simple comorbidity counts. Researchers wishing to summarize the Elixhauser comorbidities with a single value should use the VW score or those derived in this study.

Molnar, C.; Simon, E.; Kazup, A.; Gal, J.; Molnar, L.; Novak, L.; Bereczki, D.; Sessler, D. I.; Fulesdi, B.
J Neurol Sci. 2015: pp. 70-3.
ABSTRACT: OBJECTIVE: Postcraniotomy headache causes considerable pain and can be difficult to treat. We therefore tested the hypothesis that a single 100-mg preoperative dose of diclofenac reduces the intensity of postcraniotomy headache, and reduces analgesic requirements. METHODS: 200 patients having elective craniotomies were randomly assigned to diclofenac (n=100) or control (n=100). Pain severity was assessed by an independent observer using a 10-cm-long visual analog scale the evening of surgery, and on the 1st and 5th postoperative days. Analgesics given during the first five postoperative days were converted to intramuscular morphine equivalents. Results were compared using Mann-Whitney-tests; P<0.05 was considered statistically significant. RESULTS: Baseline and surgical characteristics were comparable in the diclofenac and control groups. Visual analog pain scores were slightly, but significantly lower with diclofenac at all times (means and 95% confidence intervals): the evening of surgery, 2.47 (1.8-3.1) vs. 4. 37 (5.0-3.7), (P<0.001); first postoperative day, 3.98 (3.4-4.6) vs. 5.6 (4.9-6.2) cm (P<0.001) and 5th postoperative day: 2.8 (2.2-3.4) vs. 4.0+/-(3.3-4.7) cm (P=0.013). Diclofenac reduced systemic analgesic requirements over the initial five postoperative days (mean and 95% CI): 3.3 (2.6-3.9) vs. 4.3 (3.5-5.1) mg morphine equivalents (P<0.05). CONCLUSIONS: Preoperative diclofenac administration reduces postcraniotomy headache and postoperative analgesic requirements - a benefit that persisted throughout five postoperative days.

Isik, B.; Yaman, S.; Aktuna, S.; Turan, A.
Analgesic efficacy of prophylactic gabapentin and lornoxicam in preventing postendodontic pain [no abstract available]
Pain Medicine. 2015

Sonny, A.; Avitsian, R.; Hussain, M. S.; Elsharkawy, H.
J Clin Anesth. 2015: pp. 170-4.
ABSTRACT: A 68-year-old woman with acute ischemic stroke presented for mechanical thrombectomy, after failed thrombolysis with intravenous recombinant tissue plasminogen activator. The procedure was completed successfully with dexmedetomidine infusion. However, she developed acute angioedema toward the end of the procedure requiring emergent fiberoptic-guided endotracheal intubation. Angioedema has been reported to occur after administering intravenous recombinant tissue plasminogen activator with an incidence of 1.3%-5.1% in patients with acute stroke.

Komatsu, R.; Makarova, N.; Dalton, J. E.; Sun, Z.; Chang, D.; Grandhe, R.; Sreedharan, R.; De Oliveira Dias, K.; Pal, R.; Bashour, A.; Murthy, S. C.; Turan, A.
J Anesth. 2015: pp. 47-55.
ABSTRACT: PURPOSE: Atrial arrhythmias are common after non-cardiac thoracic surgery. We tested the hypothesis that TEA reduces the risk of new-onset atrial arrhythmias after pulmonary resection. METHODS: We evaluated patients who had pulmonary resection. New-onset atrial arrhythmias detected before hospital discharge was our primary outcome. Secondary outcomes included other cardiovascular complications, pulmonary complications, time-weighted average pain score over 72 h, and duration of hospitalization. Patients with combination of general anesthesia and TEA were matched on propensity scores with patients given general anesthesia only. The matched groups were compared by use of logistic regression, linear regression, or Cox proportional hazards regression, as appropriate. RESULTS: Among 1,236 patients who had pulmonary resections, 937 received a combination of general anesthesia and TEA (TEA) and 299 received general anesthesia only (non-TEA). We successfully matched 311 TEA patients with 132 non-TEA patients. We did not find a significant association between TEA and postoperative atrial arrhythmia (odds ratio (95 % CI) of 1.05 (0.50, 2.19), P = 0.9). TEA was not significantly associated with length of hospital stay or postoperative pulmonary complications (odds ratio (95 % CI) of 0.71 (0.22, 2.29), P = 0.47). TEA patients experienced fewer postoperative cardiovascular complications; although the association was not statistically significant (odds ratio (95 % CI) of 0.30 (0.06, 1.45), P = 0.06). Time-weighted average pain scores were similar in the two groups. CONCLUSION: TEA was not associated with reduced occurrence of postoperative atrial arrhythmia. Although postoperative pulmonary complications were similar with and without TEA, TEA patients tended to experience fewer cardiovascular complications.

Nash, D. M.; Mustafa, R. A.; McArthur, E.; Wijeysundera, D. N.; Paterson, J. M.; Sharan, S.; Vinden, C.; Wald, R.; Welk, B.; Sessler, D. I.; Devereaux, P. J.; Walsh, M.; Garg, A. X.
Can J Anaesth. 2015: pp. 356-368.
ABSTRACT: PURPOSE: To determine whether combining spinal or epidural anesthesia with general anesthesia (combined anesthesia) reduces major medical complications of elective surgery compared with general anesthesia alone. METHODS: We conducted a propensity-matched population-based historical cohort study using large healthcare databases from Ontario, Canada. We identified patients undergoing 21 different elective procedures that were amenable to either combined anesthesia or general anesthesia alone in 108 hospitals from 2004 to 2011. We assessed the following four outcomes together as a composite and individually in the 30 days following surgery: acute kidney injury, stroke, myocardial infarction, and all-cause mortality. RESULTS: Prior to matching, we identified 21,701 patients receiving general anesthesia and 8,042 patients receiving combined anesthesia. After matching, our cohort included 12,379 patients. Twenty-eight baseline characteristics were well-matched between the combined (n = 4,773) and general anesthesia groups (n = 7,606). Mean patient age was 66 yr. Relative to general anesthesia alone, combined anesthesia was not associated with a reduced risk for the composite outcome [104/4,773 (2.2%) vs 162/7,606 (2.1%); odds ratio (OR) 0.97; 95% confidence interval (CI) 0.75 to 1.24] or for any of the four component outcomes when examined separately: acute kidney injury (OR 0.93; 95% CI 0.58 to 1.51), stroke (OR 0.79; 95% CI 0.36 to 1.73), myocardial infarction (OR 1.04; 95% CI 0.69 to 1.57), and all-cause mortality (OR 0.91; 95% CI 0.59 to 1.42). CONCLUSION: The addition of spinal or epidural anesthesia to general anesthesia was not associated with a reduced risk of major medical complications among 21 different elective procedures when compared with general anesthesia alone.

Hansen, J. K.; Anthony, D. G.; Li, L.; Wheeler, D.; Sessler, D. I.; Bashour, C. A.
J Intensive Care Med. 2015: pp. 338-43.
ABSTRACT: PURPOSE: Postoperative positive end-expiratory pressure (PEEP) selection in patients who are mechanically ventilated after cardiac operations often seems random. The aim of this investigation was to compare the 2 most common postoperative initial PEEP settings at our institution, 8 and 5 cm H2O, on postoperative initial tracheal intubation time (primary outcome); cardiovascular intensive care unit (CVICU); hospital length of stay (LOS); occurrence of pneumonia; and hospital mortality (secondary outcomes). MATERIALS AND METHODS: The electronic medical records of patients who were mechanically ventilated after isolated coronary artery bypass grafting (CABG) or combined CABG and valve operations were reviewed. Propensity score matching was used to compare patients with an initial postoperative PEEP setting of 8 cm H2O (n = 4722 [25.9%]) with those who had PEEP of 5 cm H2O (n = 13 535 [74.1%]) on the primary and secondary outcomes listed earlier. RESULTS: There was no difference in initial postoperative intubation time between the PEEP of 8 cm H2O and the PEEP of 5 cm H2O patient groups (mean 11.9 vs 12.0 hours [median 8.2 vs 8.8 hours], P = .89). The groups did not differ on the occurrence of pneumonia (0.43% vs 0.60%, P = .25) nor on hospital mortality (0.47% vs 0.43%, P = .76). Aspiration pneumonia occurrence approached a significant difference (0.06% vs 0.21%, P value = .052), as did CVICU LOS (mean: 47.9 vs 49.8 hours [median: 28.5 vs 28.4 hours], P = .057), but were not statistically different. There was a slight but likely clinically unimportant difference in hospital LOS (7.7 vs 7.4 days, PEEP = 8 vs 5, P < .001). CONCLUSION: Patients being mechanically ventilated after cardiac operations with an initial postoperative PEEP setting of 8 versus 5 cm H2O differed significantly only on hospital LOS but the difference was likely clinically unimportant. Thus, use of 8 cm H2O PEEP in these patients without a clinical indication, although likely not harmful, does not seem beneficial.

Koyuncu, O.; Turhanoglu, S.; Ozbakis Akkurt, C.; Karcioglu, M.; Ozkan, M.; Ozer, C.; Sessler, D. I.; Turan, A.
J Clin Anesth. 2015: pp. 51-6.
ABSTRACT: STUDY OBJECTIVE: To determine whether the new selective binding agent sugammadex causes less postoperative nausea and vomiting (PONV) than the cholinesterase inhibitor neostigmine. DESIGN: Prospective, randomized, double-blinded study. SETTING: University-affiliated hospital. PATIENTS: One hundred American Society of Anesthesiologists physical status 1 and 2 patients scheduled for extremity surgery. INTERVENTIONS: Patients were randomly assigned to neostigmine (70 mug/kg) and atropine (0.4 mg per mg neostigmine) or sugammadex 2 mg/kg for neuromuscular antagonism at the end of anesthesia, when 4 twitches in response to train-of-four stimulation were visible with fade. MEASUREMENTS: We recorded PONV, recovery parameters, antiemetic consumption, and side effects. MAIN RESULTS: Nausea and vomiting scores were lower in the sugammadex patients upon arrival in the postanesthesia care unit (med: 0 [min-max, 0-3] vs med: 0 [min-max, 0-3]; P < .05), but thereafter low and comparable. Postoperative antiemetic and analgesic consumption were similar in each group. Extubation (median [interquartile range], 3 [1-3.25] vs 4 [1-3.25]; P < .001) first eye opening (4 [3-7.25] vs 7 [5-11]; P < .001), and head lift (4 [2-7.25] vs 8 [11-25]; P < .001) in minutes were shorter in patients given sugammadex. Postoperative heart rates were significantly lower in all measured times patients given neostigmine. CONCLUSIONS: Nondepolarizing neuromuscular blocking antagonism with sugammadex speeds recovery of neuromuscular strength but only slightly and transiently reduces PONV compared with neostigmine and atropine.

Buggy, D. J.; Borgeat, A.; Cata, J.; Doherty, D. G.; Doornebal, C. W.; Forget, P.; Gottumukkala, V.; Gottschalk, A.; Gupta, A.; Gupta, K.; Hales, T. G.; Hemmings, H. C.; Hollmann, M. W.; Kurz, A.; Ma, D.; Parat, M. O.; Sessler, D. I.; Shorten, G.; Singleton, P.
Consensus statement from the BJA Workshop on Cancer and Anaesthesia [no abstract available]
Br J Anaesth. 2015: pp. 2-3.

Sztain, J. F.; Machi, A. T.; Kormylo, N. J.; Abramson, W. B.; Madison, S. J.; Monahan, A. M.; Khatibi, B.; Ball, S. T.; Gonzales, F. B.; Sessler, D. I.; Mascha, E. J.; You, J.; Nakanote, K. A.; Ilfeld, B. M.
Reg Anesth Pain Med. 2015: pp. 559-67.
ABSTRACT: BACKGROUND: We tested the hypothesis that, following unicompartment knee arthroplasty, a continuous adductor canal block decreases the time to reach 4 discharge criteria compared with a continuous femoral nerve block. METHODS: Subjects were randomized to either an adductor canal or femoral perineural catheter (2-day ropivacaine 0.2% infusion) in an unmasked fashion. The primary outcome was the time to attain 4 discharge criteria: (1) adequate analgesia; (2) intravenous opioid independence; (3) ability to independently stand, walk 3 m, return, and sit down; and (4) ambulate 30 m. RESULTS: Subjects with an adductor canal catheter (n = 15) reached all 4 criteria in a median of 35 hours (interquartile range, 24-43 hours), compared with 40 hours (interquartile range, 27-69 hours) for those with a femoral catheter (n = 15; Wilcoxon rank sum test: P = 0.46; log-rank test: P = 0.16). However, the percentages of subjects (adductor canal: femoral) who reached the 2 mobilization criteria were 27%:0% on postoperative day (POD) 0, 93%:53% on POD 1, and 100%:73% on POD 2. Of adductor canal subjects, 100% were discharge ready by POD 2, compared with only 73% of femoral subjects (P < 0.001). CONCLUSIONS: Compared with a continuous femoral nerve block, a continuous adductor canal block did not appreciably decrease the median number of hours to overall discharge readiness, yet did decrease the number of discrete days until discharge readiness. These results are applicable to only unicompartment knee arthroplasty and must be considered preliminary because of the limited sample size of this pilot study.

Machi, A. T.; Sztain, J. F.; Kormylo, N. J.; Madison, S. J.; Abramson, W. B.; Monahan, A. M.; Khatibi, B.; Ball, S. T.; Gonzales, F. B.; Sessler, D. I.; Mascha, E. J.; You, J.; Nakanote, K. A.; Ilfeld, B. M.
Anesthesiology. 2015: pp. 444-56.
ABSTRACT: BACKGROUND: The authors conducted a randomized, controlled, parallel-arm, superiority study to test the hypothesis that a continuous adductor canal block decreases the time to attain four discharge criteria compared with a continuous femoral nerve block after tricompartment knee arthroplasty. METHODS: Subjects undergoing tricompartment knee arthroplasty were randomized using computer-generated lists to either an adductor canal or femoral perineural catheter (3-day ropivacaine 0.2% infusion) in an unmasked manner. The primary outcome was the time to attain four criteria: (1) adequate analgesia; (2) intravenous opioids independence; (3) ability to stand, walk 3 m, return, and sit down; and (4) ambulate 30 m. RESULTS: Subjects with an adductor canal catheter (n = 39) reached all four criteria in a median of 55 h (interquartile, 42 to 63 h) compared with 61 h (49 to 69 h) for those with a femoral catheter (n = 41; 95% CI, -13 to 1 h; P = 0.12). The percentage of subjects who reached the two mobilization criteria on postoperative days 1 and 2 were 72 and 95% for those with an adductor canal catheter (n = 39), but only 27 and 76% in subjects with a femoral catheter (n = 41; both P < 0.001). Differences in pain scores at rest and intravenous opioid requirements were minimal, but femoral infusion improved dynamic analgesia (P = 0.01 to 0.02). CONCLUSION: Compared with a continuous femoral nerve block, a continuous adductor canal block did not appreciably decrease the time to overall discharge readiness even though it did decrease the time until adequate mobilization, primarily because both groups experienced similar analgesia and intravenous opioid requirements that-in most cases-exceeded the time to mobilization.

Koyuncu, O.; Turhanoglu, S.; Tuzcu, K.; Karcioglu, M.; Davarci, I.; Akbay, E.; Cevik, C.; Ozer, C.; Sessler, D. I.; Turan, A.
Paediatr Anaesth. 2015: pp. 247-52.
ABSTRACT: BACKGROUND: Carbon monoxide (CO) is a product of burning solid fuel in stoves and smoking. Exposure to CO may provoke postoperative complications. Furthermore, there appears to be an association between COHb concentrations and pain. We thus tested the primary hypothesis that children with high preoperative carboxyhemoglobin (COHb) concentrations have more postoperative complications and pain after tonsillectomies, and secondarily that high-COHb concentrations are associated with more pain and analgesic use. METHODS: 100 children scheduled for elective tonsillectomy were divided into low and high carbon monoxide (CO) exposure groups: COHb /=4 g.dl(-1) . We considered a composite of complications during the 7 days after surgery which included bronchospasm, laryngospasm, persistent coughing, desaturation, re-intubation, hypotension, postoperative bleeding, and reoperation. Pain was evaluated with Wong-Baker Faces pain scales, and supplemental tramadol use recorded for four postoperative hours. RESULTS: There were 36 patients in the low-exposure group COHb [1.8 +/- 1.2 g.dl(-1) ], and 64 patients were in the high-exposure group [6.4 +/- 2.1 g.dl(-1) ]. Indoor coal-burning stoves were reported more often by families of the high- than low-COHb children (89% vs 72%, P < 0.001). Second-hand cigarette smoke exposure was reported by 54% of the families with children with high COHb, but only by 24% of the families of children with low COHb. Composite complications were more common in patients with high COHb [47% vs 14%, P = 0.0001, OR:7.4 (95% Cl, lower = 2.5-upper = 21.7)], with most occurring in the postanesthesia care unit. Pain scores in postanesthesia care unit and one hour after surgery were statistically significantly lower in the low-exposure group [respectively, P = 0.020 (95%CI, lower = -1.21-upper = -0.80), P = 0.026 (95% CI, lower = -0.03-upper = 0.70)], and tramadol use increased at 4 h (3.5 (interquartile range: 0-8) vs 6 (5-9) mg, P = 0.012) and 24 h (3.5 (0-8) vs 6 (5-9) mg, P = 0.008). CONCLUSION: High preoperative COHb concentrations are associated with increased postoperative complications and pain.

Cywinski, J. B.; Mascha, E. J.; Kurz, A.; Sessler, D. I.
Can J Anaesth. 2015: pp. 745-752.
ABSTRACT: BACKGROUND: Serum creatinine is the most commonly used indicator of renal function, but its derivative, estimated glomerular filtration rate (eGFR), has been shown to be superior in non-surgical settings. It remains unknown if eGFR better predicts postoperative mortality in non-cardiac surgical patients. We thus tested the hypothesis that eGFR predicts 30-day mortality after non-cardiac surgery better than serum creatinine. METHODS: We evaluated patients who had inpatient non-cardiac surgery of at least one hour duration during January 2006 to December 2011 at the Cleveland Clinic Main Campus and whose preoperative serum creatinine was measured within 30 days before surgery. The eGFR was calculated using the Chronic Kidney Disease-Epidemiology Collaboration equation. Preoperative eGFR was compared in a multivariable analysis with preoperative serum creatinine (both assessed as continuous variables) on the ability to predict 30-day mortality in all patients. Secondarily, the comparison was made within subgroups based on amount of blood loss, blood transfusion, and sex. RESULTS: There were 92,888 patients included in the final analysis. The eGFR was a modestly better discriminator of 30-day mortality than serum creatinine, with an estimated c-statistic (95% confidence interval) of 0.67 (0.65 to 0.68) for eGFR vs 0.61 (0.59 to 0.63) for serum creatinine (P < 0.001). Furthermore, the eGFR was consistently a better discriminator of 30-day mortality across blood loss, transfusion, and sex groups. Reclassification analyses suggested improved individual predictions of 30-day mortality using eGFR compared with serum creatinine. Nevertheless, a multivariable combination of baseline characteristics of American Society of Anesthesiologists physical status, age, and body mass index (all P < 0.001) discriminated 30-day mortality with a c-statistic of 0.850. Adding eGFR to the model improved the c-statistic to only 0.851, while separately adding serum creatinine did not change the c-statistic. CONCLUSION: The eGFR is a modestly better predictor of 30-day mortality than serum creatinine in patients having inpatient non-cardiac surgery. Given that eGFR is often reported by clinical laboratories and is otherwise easy to calculate, it should generally be used in preference to creatinine alone.

Liu, N.; Lory, C.; Assenzo, V.; Cocard, V.; Chazot, T.; Le Guen, M.; Sessler, D. I.; Journois, D.; Fischler, M.
Br J Anaesth. 2015: pp. 605-14.
ABSTRACT: BACKGROUND: We used an automated bispectral index (BIS)-guided dual-loop controller to determine propofol and remifentanil requirements during general anaesthesia in obese and lean surgical patients. METHODS: Obese patients, BMI>35 kg m(-2), and lean patients (<25 kg m(-2)) having laparoscopic procedures were prospectively evaluated in this multicentre single-blind study. The automated controller targeted BIS between 40 and 60 by adjusting propofol and remifentanil administration. Propofol and remifentanil consumptions were calculated using both total body weight (TBW) and ideal body weight (IBW). Results are expressed as medians (inter-quartile range). RESULTS: Thirty obese [BMI=43 (40-49) kg m(-2)] and 29 lean [BMI=23 (21-25) kg m(-2)] patients completed the study. BIS was between 40 and 60 during 84 (69-91)% vs 85 (78-92)% of the anaesthetic time, P=0.46. The amount of propofol given during induction [1.2 (1.1-1.6) vs 1.3 (1.0-1.7) mg kg(-1), P=0.47] and maintenance [5.2 (4.1-6) vs 5.3 (4.7-6.4) mg kg(-1) h(-1), P=0.39] calculated using TBW was similar between the two groups. The dual-loop controller delivered half as much remifentanil to the obese patients during induction [1.0 (0.8-1.6) vs 2.2 (1.5-2.7) microg kg(-1), P<0.001] and maintenance [0.12 (0.07-0.16) vs 0.25 (0.17-0.29) microg kg(-1) min(-1), P<0.001] calculated using TBW. But when remifentanil consumption was calculated using IBW, the amounts were similar during induction at 2.2 (1.6-3.5) vs 2.0 (1.6-3.0) microg kg(-1) IBW, P=0.48, and during maintenance at 0.26 (0.16-0.34) vs 0.27 (0.18-0.33 ) microg kg(-1) min(-1), P=0.50. CONCLUSIONS: The amount of propofol-remifentanil administered by the controller is consistent with current knowledge, propofol is best dosed using TBW whereas remifentanil is best dosed using IBW. CLINICAL TRIAL REGISTRATION: NCT00779844.

Orliaguet, G. A.; Benabbes Lambert, F.; Chazot, T.; Glasman, P.; Fischler, M.; Liu, N.
Anesthesiology. 2015: pp. 759-67.
ABSTRACT: BACKGROUND: This study was designed to assess the feasibility of dual closed-loop titration of propofol and remifentanil guided solely by the Bispectral Index (BIS) monitor in pediatric and adolescent patients during anesthesia. METHODS: Children undergoing elective surgery in this single-blind randomized study were allocated into the closed-loop (auto) or manual (manual) group. Primary outcome was the percentage of time with the BIS in the range 40 to 60 (BIS40-60). Secondary outcomes were the percentage of deep (BIS<40) anesthesia and drug consumption. Data are presented as median (interquartile range) or number (%). RESULTS: Twenty-three patients (12 [10 to 14] yr) were assigned to the auto group and 19 (14 [7 to 14] yr) to the manual group. The closed-loop controller was able to provide induction and maintenance for all patients. The percentage of time with BIS40-60 was greater in the auto group (87% [75 to 96] vs. 72% [48 to 79]; P = 0.002), with a decrease in the percentage of BIS<40 (7% [2 to 17] vs. 21% [11 to 38]; P = 0.002). Propofol (2.4 [1.9 to 3.3] vs. 1.7 [1.2 to 2.8] mg/kg) and remifentanil (2.3 [2.0 to 3.0] vs. 2.5 [1.2 to 4.3] mug/kg) consumptions were similar in auto versus manual groups during induction, respectively. During maintenance, propofol consumption (8.2 [6.0 to 10.2] vs. 7.9 [7.2 to 9.1] mg kg h; P = 0.89) was similar between the two groups, but remifentanil consumption was greater in the auto group (0.39 [0.22 to 0.60] vs. 0.22 [0.17 to 0.32] mug kg min; P = 0.003). Perioperative adverse events and length of stay in the postanesthesia care unit were similar. CONCLUSION: Intraoperative automated control of hypnosis and analgesia guided by the BIS is clinically feasible in pediatric and adolescent patients and outperformed skilled manual control.

Duncan, A. E.; Kateby Kashy, B.; Sarwar, S.; Singh, A.; Stenina-Adognravi, O.; Christoffersen, S.; Alfirevic, A.; Sale, S.; Yang, D.; Thomas, J. D.; Gillinov, M.; Sessler, D. I.
Anesthesiology. 2015: pp. 272-287.
ABSTRACT: BACKGROUND: Glucose-insulin-potassium (GIK) administration during cardiac surgery inconsistently improves myocardial function, perhaps because hyperglycemia negates the beneficial effects of GIK. The hyperinsulinemic normoglycemic clamp (HNC) technique may better enhance the myocardial benefits of GIK. The authors extended previous GIK investigations by (1) targeting normoglycemia while administering a GIK infusion (HNC); (2) using improved echocardiographic measures of myocardial deformation, specifically myocardial longitudinal strain and strain rate; and (3) assessing the activation of glucose metabolic pathways. METHODS: A total of 100 patients having aortic valve replacement for aortic stenosis were randomly assigned to HNC (high-dose insulin with concomitant glucose infusion titrated to normoglycemia) versus standard therapy (insulin treatment if glucose >150 mg/dl). The primary outcomes were left ventricular longitudinal strain and strain rate, assessed using speckle-tracking echocardiography. Right atrial tissue was analyzed for activation of glycolysis/pyruvate oxidation and alternative metabolic pathways. RESULTS: Time-weighted mean glucose concentrations were lower with HNC (127 +/- 19 mg/dl) than standard care (177 +/- 41 mg/dl; P < 0.001). Echocardiographic data were adequate in 72 patients for strain analysis and 67 patients for strain rate analysis. HNC did not improve myocardial strain, with an HNC minus standard therapy difference of -1.2% (97.5% CI, -2.9 to 0.5%; P = 0.11). Strain rate was significantly better, but by a clinically unimportant amount: -0.16 s (-0.30 to -0.03 s; P = 0.007). There was no evidence of increased glycolytic, pyruvate oxidation, or hexosamine biosynthetic pathway activation in right atrial samples (HNC, n = 20; standard therapy, 22). CONCLUSION: Administration of glucose and insulin while targeting normoglycemia during aortic valve replacement did not meaningfully improve myocardial function.

Elsharkawy, H.; Salmasi, V.; Abd-Elsayed, A.; Turan, A.
J Clin Anesth. 2015
ABSTRACT: BACKGROUND: Optimum positioning of the nerve catheter is crucial for a successful nerve block. We present a novel technique for confirmation of catheter position. METHODS: We are describing a novel technique for localization of the shaft and tip of the peripheral nerve catheter. After introduction of the catheter 3 to 5 cm beyond the needle tip and removal of the needle, the guide wire was reintroduced and was moved inward and outward rapidly. This movement produced the color Doppler effect along the track of the catheter and the catheter tip that helped us verify the proper positioning of the catheter. RESULTS: We used our technique in a cadaveric study for bilateral supraclavicular brachial plexus block, followed by a series of 5 patients undergoing femoral, sciatic (anterior approach), popliteal (2 patients), and brachial plexus blocks. Catheters were also identified on M-Mode sonography during pumping maneuver and during the injection of medications. CONCLUSION: Pumping maneuver and M-Mode can be additional tools in the array of modalities applied to verify proper positioning of a nerve catheter.

Saager, L.; Turan, A.; Egan, C.; Mascha, E. J.; Kurz, A.; Bauer, M.; Besson, H.; Sessler, D. I.; Hesler, B. D.
Anesthesiology. 2015: pp. 551-9.
ABSTRACT: BACKGROUND: Previously reported incidences for intraoperative hypersensitivity reactions vary more than 15-fold. The goal was to determine the incidence of intraoperative hypersensitivity events at a U.S. surgical center. METHODS: With institutional review board (Cleveland, Ohio) approval and waiver of written/informed consent, the anesthesia records of adult patients undergoing noncardiac surgery from 2005 to 2011 at the Cleveland Clinic were queried using a novel electronic search protocol developed to identify potential hypersensitivity reactions: cardiovascular collapse defined as systolic arterial blood pressure less than 50 mmHg; administration of epinephrine; administration of diphenhydramine; physician comments in the anesthesia record suggestive of hypersensitivity reactions; laboratory tests for histamine, tryptase, or immunoglobulin-E within 24 h of surgery; and International Classification of Diseases, Ninth Revision, codes suggestive of hypersensitivity reactions. Each electronically identified candidate chart was evaluated by an adjudication committee. Hypersensitivity reactions were graded on a 5-point severity scale. From these data, the authors determined the proportion of operations having adjudicated hypersensitivity reactions, and calculated the 95% exact binomial CI. RESULTS: Among 178,746 records, 4,008 charts were identified by the search strategies. After adjudication, 264 hypersensitivity cases were identified. The overall incidence of hypersensitivity reactions was 1:677 surgeries, corresponding to 15 (95% CI, 13 to 17) cases per 10,000 operations. The incidence of severe hypersensitivity reactions (grades 3 to 5) was 1:4,583, corresponding to 2 (95% CI, 2 to 3) cases per 10,000 operations. CONCLUSIONS: The incidence of severe hypersensitivity reactions was similar to previous reports. However, the overall incidence of hypersensitivity reactions was much greater than reported elsewhere, possibly because of a comprehensive search strategy.

Sun, Z.; Honar, H.; Sessler, D. I.; Dalton, J. E.; Yang, D.; Panjasawatwong, K.; Deroee, A. F.; Salmasi, V.; Saager, L.; Kurz, A.
Anesthesiology. 2015: pp. 276-85.
ABSTRACT: BACKGROUND: Core temperature patterns in patients warmed with forced air remain poorly characterized. Also unknown is the extent to which transient and mild intraoperative hypothermia contributes to adverse outcomes in broad populations. METHODS: We evaluated esophageal (core) temperatures in 58,814 adults having surgery lasting >60 min who were warmed with forced air. Independent associations between hypothermic exposure and transfusion requirement and duration of hospitalization were evaluated. RESULTS: In every percentile subgroup, core temperature decreased during the first hour and subsequently increased. The mean lowest core temperature during the first hour was 35.7 +/- 0.6 degrees C. Sixty-four percent of the patients reached a core temperature threshold of <36 degrees C 45 min after induction; 29% reached a core temperature threshold of <35.5 degrees C. Nearly half the patients had continuous core temperatures <36 degrees C for more than an hour, and 20% of the patients were <35.5 degrees C for more than an hour. Twenty percent of patients had continuous core temperatures <36 degrees C for more than 2 h, and 8% of the patients were below 35.5 degrees C for more than 2 h. Hypothermia was independently associated with both transfusions and duration of hospitalization, although the prolongation of hospitalization was small. CONCLUSIONS: Even in actively warmed patients, hypothermia is routine during the first hour of anesthesia. Thereafter, average core temperatures progressively increase. Nonetheless, intraoperative hypothermia was common, and often prolonged. Hypothermia was associated with increased transfusion requirement, which is consistent with numerous randomized trials.

Mascha, E. J.; Yang, D.; Weiss, S.; Sessler, D. I.
Anesthesiology. 2015: pp. 79-91.
ABSTRACT: BACKGROUND: Little is known about the relationship between intraoperative blood pressure variability and mortality after noncardiac surgery. Therefore, the authors tested the hypothesis that blood pressure variability, independent from absolute blood pressure, is associated with increased 30-day mortality. METHODS: Baseline and intraoperative variables plus 30-day mortality were obtained for 104,401 adults having noncardiac surgery lasting 60 min or longer. In confounder-adjusted models, the authors evaluated the associations between 30-day mortality and both time-weighted average intraoperative mean arterial pressure (TWA-MAP) and measures of intraoperative MAP variability-including generalized average real variability of MAP (ARV-MAP) and SD of MAP (SD-MAP). RESULTS: Mean +/- SD TWA-MAP was 84 +/- 10 mmHg, and ARV-MAP was 2.5 +/- 1.3 mmHg/min. TWA-MAP was strongly related to 30-day mortality, which more than tripled as TWA-MAP decreased from 80 to 50 mmHg. ARV-MAP was only marginally related to 30-day mortality (P = 0.033) after adjusting for TWA-MAP. Compared with median ARV-MAP, odds ratio (95% CI) for 30-day mortality was 1.14 (1.03 to 1.25) for low ARV-MAP (first quartile) and 0.94 (0.88 to 0.99) for high ARV-MAP (third quartile). Odds of 30-day mortality decreased as five-level categorized ARV-MAP increased (0.92; 0.87 to 0.99 for one category increase; P = 0.015). Secondarily, cumulative duration of MAP less than 50, 55, 60, 70, and 80 mmHg was associated with increased odds of 30-day mortality (all P < 0.001). CONCLUSION: Although lower mean arterial pressure is strongly associated with mortality, lower intraoperative blood pressure variability per se is only mildly associated with postoperative mortality after noncardiac surgery.

Saager, L.; Duncan, A. E.; Yared, J. P.; Hesler, B. D.; You, J.; Deogaonkar, A.; Sessler, D. I.; Kurz, A.
Anesthesiology. 2015: pp. 1214-23.
ABSTRACT: BACKGROUND: Postoperative delirium is common in patients recovering from cardiac surgery. Tight glucose control has been shown to reduce mortality and morbidity. Therefore, the authors sought to determine the effect of tight intraoperative glucose control using a hyperinsulinemic-normoglycemic clamp approach on postoperative delirium in patients undergoing cardiac surgery. METHODS: The authors enrolled 198 adult patients having cardiac surgery in this randomized, double-blind, single-center trial. Patients were randomly assigned to either tight intraoperative glucose control with a hyperinsulinemic-normoglycemic clamp (target blood glucose, 80 to 110 mg/dl) or standard therapy (conventional insulin administration with blood glucose target, <150 mg/dl). Delirium was assessed using a comprehensive delirium battery. The authors considered patients to have experienced postoperative delirium when Confusion Assessment Method testing was positive at any assessment. A positive Confusion Assessment Method was defined by the presence of features 1 (acute onset and fluctuating course) and 2 (inattention) and either 3 (disorganized thinking) or 4 (altered consciousness). RESULTS: Patients randomized to tight glucose control were more likely to be diagnosed as being delirious than those assigned to routine glucose control (26 of 93 vs. 15 of 105; relative risk, 1.89; 95% CI, 1.06 to 3.37; P = 0.03), after adjusting for preoperative usage of calcium channel blocker and American Society of Anesthesiologist physical status. Delirium severity, among patients with delirium, was comparable with each glucose management strategy. CONCLUSION: Intraoperative hyperinsulinemic-normoglycemia augments the risk of delirium after cardiac surgery, but not its severity.

Schuepbach, R.; Grande, B.; Camen, G.; Schmidt, A. R.; Fischer, H.; Sessler, D. I.; Seifert, B.; Spahn, D. R.; Ruetzler, K.
Can J Anaesth. 2015: pp. 762-769.
ABSTRACT: INTRODUCTION: Double-lumen endotracheal tubes (DLTs), which are commonly used for single-lung ventilation during surgery, are difficult to insert. In addition, they often move during surgical lung manipulation which can cause life-threatening complications. Flexible bronchoscopy is used routinely to establish and confirm proper DLT placement. The newly designed VivaSight DLT has an integrated camera, allowing continuous visualization of its position in the trachea. We hypothesized that the time to intubation using the VivaSight DLT would be faster than with a conventional DLT. METHODS: We enrolled 40 adults scheduled for thoracic surgery. Patients were randomized to conventional DLT (n = 20) or VivaSight DLT (n = 20). Time to intubation was our primary outcome. Secondary outcomes were insertion success without flexible bronchoscopy, frequency of tube displacement, ease of insertion, quality of lung collapse, postoperative complaints, and airway injuries. RESULTS: Time [mean (SD)] to successful intubation was significantly faster with the VivaSight DLT [63 (58) sec] compared with the conventional DLT [97 (84) sec; P = 0.03]. The VivaSight DLTs were correctly inserted during all attempts. When malpositioning of the VivaSight DLT occurred, it was easily remedied, even in the lateral position. The devices were comparable with respect to postoperative coughing, hoarseness, and sore throat. Airway injuries tended to be more common with the VivaSight DLT, although this study was underpowered for airway injuries. CONCLUSION: The VivaSight DLT camera allowed faster insertion and facilitated initial positioning. It also confirmed proper tube positioning intraoperatively and facilitated repositioning when necessary. This trial was registered at clinicaltrials.gov: NCT01807676.

Vrooman, B.; Kapural, L.; Sarwar, S.; Mascha, E. J.; Mihaljevic, T.; Gillinov, M.; Qavi, S.; Sessler, D. I.
Pain Med. 2015: pp. 1610-21.
ABSTRACT: OBJECTIVES: To test the hypotheses that lidocaine 5% patches decrease the severity of acute pain and incidence of persistent incisional pain after robotic cardiac valve surgery. DESIGN: A randomized, placebo-controlled, double-blind trial. SETTING: Tertiary care academic medical center. SUBJECTS: Patients having robotic cardiac valve surgery. METHODS: Patients having robotic cardiac valve surgery were randomly assigned to 5% lidocaine patches or identical-appearing placebo patches. Patches were applied around each incision 12 hours/day until pain resolved, or for 6 months. Supplemental opioid was provided by patient-controlled analgesia or orally. Pain was initially evaluated with a Visual Analog Scale, and subsequently by telephone with a Verbal Response Scale and the Pain Disability Index (our primary outcome) after 1 week, 1 month, 3 months, and 6 months. Global Perceived Effect, a measure of patient satisfaction, was simultaneously recorded. Repeated-measures analysis of variance and generalized estimating equations were our primary statistical tools. RESULTS: Acute pain scores and opioid use were low, as was the incidence of persistent pain. Lidocaine 5% patches did not influence any measure of acute or persistent incisional pain. Estimated difference (95% CI) in mean Pain Disability Index for Lidocaine patch minus placebo was -2.5 (95% CI -7.1, 2.1), P = 0.28. CONCLUSIONS: Lidocaine 5% patches did not reduce acute or persistent pain in patients having robotic thoracic surgery, though pain scores were low in both treatment groups. Clinicians should choose alternative analgesic approaches in these patients.

Bose, S.; Khanna, A.; You, J.; Arora, L.; Qavi, S.; Turan, A.
Can J Anaesth. 2015: pp. 770-776.
ABSTRACT: PURPOSE: Vitamin D deficiency has been associated with chronic non-specific musculoskeletal pain syndromes; however, studies are lacking with respect to its relationship with postoperative pain. We tested the hypothesis that a lower preoperative vitamin D level is associated with increased postoperative pain and/or opioid consumption in morbidly obese patients who had laparoscopic bariatric surgery. METHODS: Data from 185 patients who underwent laparoscopic bariatric surgery at the Cleveland Clinic from 2005-2009 and had a vitamin D level checked within three months of their surgery were included in the analysis. We assessed the relationship between vitamin D levels and the time-weighted average (TWA) of pain scores and total opioid consumption using multivariable regression models adjusted for potential confounders. As a secondary analysis, we compared the TWA of pain scores and opioid consumption between patients who were vitamin D deficient ( 20 ng.mL-1). RESULTS: The mean (SD) TWA pain score was 3.8 (1.5) and the median interquartile range [IQR] total opioid consumption (morphine equivalent) was 15.6 [18.2] mg during the first 72 hr postoperatively. The median [IQR] vitamin D concentration was 21.8 [17.1] ng.mL-1. The vitamin D level was not significantly associated with either the TWA pain score (Pearson correlation: -0.003; 97.5% confidence interval [CI]: -0.17 to 0.16) or opioid consumption (Spearman correlation: -0.13; 97.5% CI: -0.30 to 0.03). After adjusting for confounders, the estimated average change in TWA pain score was 0.01 (97.5% CI: -0.08 to 0.11) for a five-unit increase in vitamin D (P = 0.77). The estimated ratio of geometric means of total opioid consumption was 0.94 (97.5% CI: 0.86 to 1.03) for a five-unit increase in vitamin D concentration (P = 0.12). No difference was found between patients with vitamin D concentrations > 20 ng.mL-1 and

Takeshita, J.; Nakayama, Y.; Nakajima, Y.; Sessler, D. I.; Ogawa, S.; Sawa, T.; Mizobe, T.
Crit Care. 2015: pp. 15.
ABSTRACT: IntroductionVenous catheterisation in paediatric patients can be technically challenging. We examined factors affecting catheterisation of invisible and impalpable peripheral veins in children and evaluated the best site for ultrasound-guided catheterisation.MethodsSystolic pressure, age, sex, and American Society of Anesthesiologists (ASA) physical status were determined in 96 children weighing < 20 kg. Vein diameter and subcutaneous depth were measured with ultrasound. Logistic regression was used to evaluate the contribution of these factors to cannulation success with (n inverted question mark= inverted question mark65) or without (n inverted question mark= inverted question mark31) ultrasound guidance. Thereafter, we randomised 196 patients for venous catheter insertion in the dorsal veins of the hand, the cephalic vein in the forearm, or the great saphenous vein. Success rates and vein diameters were evaluated using Dunn tests; insertion time, using Kaplan inverted question markMeier cumulative incidence analysis.ResultsIndependent predictors of catheterisation were ultrasound guidance (odds ratio (OR) inverted question mark= inverted question mark7.3, 95% confidence interval (CI): 2.0 to 26.0, P inverted question mark= inverted question mark0.002), vein diameter (OR inverted question mark= inverted question mark1.5 per 0.1 mm increase in diameter, 95% CI: 1.1 to 2.0, P inverted question mark= inverted question mark0.007), and ASA physical status (OR inverted question mark= inverted question mark0.4 per status 1 increase, 95% CI: 0.2 to 0.9, P inverted question mark= inverted question mark0.03). Cephalic veins were significantly larger (cephalic diameter 1.8 mm, P inverted question mark= inverted question mark0.001 versus saphenous 1.5 mm; P <0.001 versus dorsal 1.5 mm). Catheterisation success rates were significantly better at the cephalic vein than either the dorsal hand or saphenous vein (cephalic 95%, 95% CI: 89 to 100%, P <0.001 versus dorsal 69%, 95% CI: 56 to 82%; P inverted question mark= inverted question mark0.03 versus saphenous 75%, 95% CI: 64 to 86%).ConclusionsThe cephalic vein in the proximal forearm appears to be the most appropriate initial site for ultrasound-guided catheterisation in invisible and impalpable veins of paediatric patients.Trial registry numberUMIN Clinical Trials Registry as UMIN000010961. Registered on 14 June 2013.

De Oliveira, G. S., Jr.; Bialek, J. M.; Turan, A.; McCarthy, R. J.; Sessler, D. I.
Reg Anesth Pain Med. 2015: pp. 539-44.
ABSTRACT: BACKGROUND AND OBJECTIVES: Perioperative modulation of the surgical inflammatory response has been hypothesized as a viable pharmacological preventive target for the development of chronic pain after surgery. The objective of the current investigation was to evaluate an association between intravenous dexamethasone 4 to 20 mg on the day of surgery with self-reported pain in the breast or axilla 3 months or more after mastectomy. METHODS: The study was a secondary data analysis of a prospective cohort investigation. Subjects who have undergone mastectomy surgery were evaluated at least 3 months after the surgical procedure for the presence of chronic postsurgical pain using validated pain questionnaires. Binary logistic regression analysis was used to determine the odds of development of chronic postsurgical pain in subjects who did and did not receive perioperative dexamethasone. RESULTS: Three hundred ten patients were included in the study. Fifty-two patients (17%) met the IMMPACT (Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials) criteria for chronic pain in the breast and/or axillary region. Two hundred eleven (68%) of 310 subjects received perioperative dexamethasone on doses varying from 4 to 20 mg. The incidence of chronic pain in the mastectomy group who received perioperative dexamethasone was not different, 15 (15.2%) of 84 compared with 37 (17.5%) of 211 in the group who did not receive perioperative dexamethasone, difference -2% (95% confidence interval, -10 to 7; P = 0.75). CONCLUSIONS: Perioperative dexamethasone is not associated with a reduction in the incidence and/or severity of chronic postmastectomy pain. In addition, we did not detect a dose-response effect of dexamethasone on the incidence of chronic postsurgical pain.

Sun, Z.; Sessler, D. I.; Dalton, J. E.; Devereaux, P. J.; Shahinyan, A.; Naylor, A. J.; Hutcherson, M. T.; Finnegan, P. S.; Tandon, V.; Darvish-Kazem, S.; Chugh, S.; Alzayer, H.; Kurz, A.
Anesth Analg. 2015: pp. 709-715.
ABSTRACT: BACKGROUND: The incidence, severity, and duration of postoperative oxygen desaturation in the general surgical population are poorly characterized. We therefore used continuous pulse oximetry to quantify arterial oxygen saturation (SpO2) in a cross-section of patients having noncardiac surgery. METHODS: Oxygen saturation, blinded to clinicians, was recorded at 1-minute intervals in patients >45 years old for up to 48 hours after noncardiac surgery in 1250 patients from Cleveland Clinic Main Campus and 250 patients from the Juravinski Hospital. We determined (1) the cumulative minutes of raw minute-by-minute values below various hypoxemic thresholds; and (2) the contiguous duration of kernel-smoothed (sliding window) values below various hypoxemic thresholds. Finally, we compared our blinded continuous values with saturations recorded during routine nursing care. RESULTS: Eight hundred thirty-three patients had sufficient data for analyses. Twenty-one percent had >/=10 min/h with raw SpO2 values <90% averaged over the entire recording duration; 8% averaged >/=20 min/h <90%; and 8% averaged >/=5 min/h <85%. Prolonged hypoxemic episodes were common, with 37% of patients having at least 1 (smoothed) SpO2 <90% for an hour or more; 11% experienced at least 1 episode lasting >/=6 hours; and 3% had saturations <80% for at least 30 minutes. Clinical hypoxemia, according to nursing records, measured only in Cleveland Clinic patients (n = 594), occurred in 5% of the monitored patients. The nurses missed 90% of smoothed hypoxemic episodes in which saturation was <90% for at least one hour. CONCLUSIONS: Hypoxemia was common and prolonged in hospitalized patients recovering from noncardiac surgery. The SpO2 values recorded in medical records seriously underestimated the severity of postoperative hypoxemia.

Rosanna Varutti; Tommaso Setti; Tiberiu Ezri; Gianluigi Nicolosi; Gianluigi Rellini ; Matteo Cassin ; Yigal Leykin
Postoperative Takotsubo cardiomyopathy triggered by intraoperative fluid overload and acute hypertensive crisis [no abstract available]
Romanian Journal of Anaesthesia and Intensive Care. 2015: pp. 47-50.

Sessler, D. I.
Preventing respiratory depression (editorial) [no abstract available]
Anesthesiology. 2015: pp. 484-5.

Turan, A.; You, J.; Egan, C.; Fu, A.; Gazmuri, I.; Khanna, A.; Eshraghi, Y.; Ghosh, R.; Bose, S.; Qavi, S.; Arora, L.; Sessler, D. I.; Doufas, A. G.
Relationship between chronic intermittent hypoxia and intraoperative mean arterial pressure in obstructive sleep apnea in patients having laparoscopic bariatric surgery [no abstract available]
Anesthesiology. 2015: pp. 64-71.

Mulla, S. M.; Maqbool, A.; Sivananthan, L.; Lopes, L. C.; Schandelmaier, S.; Kamaleldin, M.; Hsu, S.; Riva, J. J.; Vandvik, P. O.; Tsoi, L.; Lam, T.; Ebrahim, S.; Johnston, B. C.; Olivieri, L.; Montoya, L.; Kunz, R.; Scheidecker, A.; Buckley, D. N.; Sessler, D. I.; Guyatt, G. H.; Busse, J. W.
Pain. 2015: pp. 1615-9.
ABSTRACT: The Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) has recommended that trialists evaluating treatments for chronic pain should consider reporting 9 patient-important outcome domains. We examined the extent to which clinical trials evaluating the effect of opioids for chronic non-cancer pain (CNCP) report outcome domains recommended by IMMPACT. We systematically searched electronic databases for English-language studies that randomized patients with CNCP to receive an opioid or a non-opioid control. In duplicate and independently, reviewers established the eligibility of each identified study and recorded all reported outcome domains from eligible trials. We conducted a priori regression analyses to explore factors that may be associated with IMMPACT-recommended outcome domains. Among 156 eligible trials, reporting of IMMPACT-recommended outcome domains was highly variable, ranging from 99% for pain to 7% for interpersonal functioning. Recently published trials were more likely to report the effect of treatment on physical functioning, emotional functioning, role functioning, sleep and fatigue, and participant disposition. Trials for which the corresponding author was from North America were more likely to report treatment effects on physical functioning and participant ratings of improvement and satisfaction with treatment. Trials published in higher impact journals were more likely to report treatment effects on emotional function, but less likely to report participant ratings of improvement and satisfaction with treatment. Most IMMPACT domains showed an increased rate of reporting over time, although many patient-important outcome domains remained unreported by over half of all trials evaluating the effects of opioids for CNCP.

Ezri, Tiberiu; Evron, Shmuel; Petrov, Irina; Schachter, Pinhas; Berlovitz, Yitzhak; Shimonov, Mordechai
Residual curarization and postoperative respiratory complications following laparoscopic sleeve gastrectomy. The effect of reversal agents: sugammadex vs. neostigmine [no abstract available]
J Crit Care Med. 2015

Tassonyi, E.; Pongracz, A.; Nemes, R.; Asztalos, L.; Lengyel, S.; Fulesdi, B.
Anesth Analg. 2015
ABSTRACT: BACKGROUND: Pipecuronium is a steroidal neuromuscular blocking agent. Sugammadex, a relaxant binding gamma-cyclodextrin derivative, reverses the effect of rocuronium, vecuronium, and pancuronium. We investigated whether sugammadex reverses moderate pipecuronium-induced neuromuscular blockade (NMB) and the doses required to achieve reversal. METHODS: This single-center, randomized, double-blind, 5-group parallel-arm study comprised 50 patients undergoing general anesthesia with propofol, sevoflurane, fentanyl, and pipecuronium. Neuromuscular monitoring was performed with acceleromyography (TOF-Watch SX) according to international standards. When the NMB recovered spontaneously to train-of-four count 2, patients randomly received 1.0, 2.0, 3.0, or 4.0 mg/kg of sugammadex or placebo. Recovery time from sugammadex injection to normalized train-of-four (TOF) ratio 0.9 was the primary outcome variable. The recovery time from the sugammadex injection to final T1 was the secondary end point. Postoperative neuromuscular functions were also assessed. RESULTS: Each patient who received sugammadex recovered to a normalized TOF ratio of 0.9 within 5.0 minutes (95% lower confidence interval for the lowest dose 70.1%; for all doses 90.8%) and 79% of these patients reached a normalized TOF ratio 0.9 within 2.0 minutes (95% lower confidence interval for the lowest dose 26.7%; for all doses 63.7%). T1 recovered several minutes after the TOF ratio. No residual postoperative NMB was observed. CONCLUSIONS: Sugammadex adequately and rapidly reverses pipecuronium-induced moderate NMB during sevoflurane anesthesia. Once the train-of-four count has spontaneously returned to 2 responses following pipecuronium administration, a dose of 2.0 mg/kg of sugammadex is sufficient to reverse the NMB.

Komatsu, R.; You, J.; Mascha, E. J.; Sessler, D. I.; Kasuya, Y.; Turan, A.
Anesth Analg. 2015: pp. 716-726.
ABSTRACT: BACKGROUND: We tested the hypothesis that hypothyroidism, as defined by thyroid-stimulating hormone (TSH) concentration, is associated with a severity-weighted composite of mortality and major cardiovascular and infectious complications after noncardiac surgery. METHODS: In this retrospective cohort study, we evaluated adults at the Cleveland Clinic Main Campus between 2005 and 2012, who had had available TSH concentrations within the 6 months before noncardiac surgery. Patients were categorized as (1) hypothyroid (patients who had diagnosis of hypothyroidism any time prior to surgery and increased TSH value (> 5.5 mIU/L) within 6 months prior to surgery); (2) treated (hypothyroid diagnosis and normal TSH concentrations [0.4-5.5 mIU/L]); and (3) euthyroid (no hypothyroid diagnosis and normal TSH concentrations). We conducted pairwise comparisons among the 3 groups using inverse propensity score weighting to control for observed confounding variables. Average relative effect generalized estimating equation model was used for the primary outcome composite of in-hospital cardiovascular morbidity, surgical wound complication or infection, and mortality. Logistic regression and Cox proportional hazards regression were used for secondary outcomes of intraoperative vasopressor use and duration of hospitalization, respectively. RESULTS: We identified 800 hypothyroid patients (median TSH: 8.6 mIU/L [Q1, Q3: 6.5, 13.0]), 1805 treated patients (2.0 mIU/L [1.1, 3.2]), and 5612 euthyroid patients (1.7 mIU/L [1.1, 2.6]). There were no significant differences among the hypothyroid, treated, and euthyroid patients on the primary composite outcome (all P values >/=0.30). Hypothyroid patients were slightly more likely to receive vasopressor during surgery than either treated (odds ratio, 1.17; 99.2% confidence interval [CI], 1.01-1.36) or euthyroid (odds ratio, 1.12; 99.2% CI, 1.02-1.24) patients. Furthermore, hypothyroid patients were slightly but significantly less likely to be discharged at any given postoperative time than treated patients (hazard ratio, 0.92; 99.2% CI, 0.86-0.99). CONCLUSIONS: Hypothyroidism was not associated with worse postoperative mortality, wound, or cardiovascular outcomes in noncardiac patients. Thus, postponing surgery to initiate thyroid replacement therapy in patients with hypothyroidism seems unnecessary.

Ozkan Seyhan, T.; Orhan-Sungur, M.; Basaran, B.; Savran Karadeniz, M.; Demircan, F.; Xu, Z.; Sessler, D. I.
Int J Obstet Anesth. 2015: pp. 35-40.
ABSTRACT: BACKGROUND: Increased intra-abdominal pressure in pregnancy is thought to affect intrathecal drug spread. However this assumption remains largely untested. The aim of this prospective study was to evaluate the association between intra-abdominal pressure and maximum sensory block level in parturients receiving spinal anesthesia for cesarean section. METHODS: Parturients having elective cesarean section with single-shot spinal anesthesia using hyperbaric bupivacaine 12.5mg were included. Intra-abdominal pressure was measured via a bladder catheter after establishing a T4 sensory block and at the end of surgery in the supine position with 10 degrees left lateral tilt. We recorded demographic data, descriptive characteristics of pregnancy, self-reported weight gain and weight of the newborn. As secondary outcomes, we evaluated onset of sensory block, maximum sensory block, motor block, number of hypotensive episodes, fluid and ephedrine requirements, time to first analgesic request, time to one-point recovery of motor block and side effects. RESULTS: The median value of the maximum sensory block level was T2 in 117 parturients. Median [interquartile range] pre-incision and postoperative intra-abdominal pressure were 13 [11-16] and 9 [6-10]mmHg respectively. No association was observed between maximum sensory block level and pre-incision intra-abdominal pressure (P=0.83). Weight was associated with pre-incision intra-abdominal pressure with an estimated odds ratio of 1.04 per kg (99.4% CI: 1.00-1.08). There was a moderate correlation between pre-incision and postoperative intra-abdominal pressure with a Spearman correlation coefficient of 0.67 (99.5% CI: 0.5-0.79). There was no association between pre-incision intra-abdominal pressure and secondary outcomes. CONCLUSIONS: In parturients, intra-abdominal pressure was not associated with spinal block spread, block onset time, recovery or side effects.

Ino, H.; Masamune, T.; Sato, H.; Okuyama, K.; Wada, K.; Iwashita, H.; Ishiyama, T.; Oguchi, T.; Sessler, D. I.; Matsukawa, T.
Anesth Analg. 2015: pp. 525-31.
ABSTRACT: BACKGROUND: Hyperglycemia is common in critically ill and surgical patients, as are core temperature disturbances. The effect of hyperglycemia on thermoregulatory defenses remains unknown. We determined the effect of blood glucose concentration on the shivering threshold in rabbits. METHODS: Twenty-seven rabbits lightly anesthetized with isoflurane were randomly assigned to infusions of (1) saline, (2) insulin titrated to produce blood glucose concentrations 60 to 100 mg/dL, or (3) 50% dextrose titrated to produce blood glucose concentrations 200 to 300 mg/dL. Core temperature was reduced at a rate of 2 to 3 degrees C/h by perfusing water at 10 degrees C through a plastic tube positioned in the colon. Cooling continued until shivering was observed by an investigator blinded to treatment or until esophageal (core) temperature reached 34 degrees C. Core temperatures at the onset of shivering defined the threshold. All analyses were conducted using SAS version 9.3 (SAS Institute Inc., Cary, NC). RESULTS: Rabbits given saline shivered at 37.2 +/- 0.5 degrees C (mean +/- SD). Rabbits given insulin shivered at 36.3 +/- 1.1 degrees C. Rabbits given dextrose shivered at 38.0 +/- 0.6 degrees C. The shivering threshold increased as a function of blood glucose concentration: shivering threshold ( degrees C) = 0.009 [blood glucose concentration (mg/dL)] + 35.6, r = 0.53. The shivering threshold thus increased approximately 1 degrees C for each 100 mg/dL increase in blood glucose concentration. CONCLUSIONS: Hyperglycemia increases the threshold for shivering, whereas hypoglycemia lowers the threshold on rabbits.

Ishiyama, T.; Kotoda, M.; Asano, N.; Ikemoto, K.; Mitsui, K.; Sato, H.; Matsukawa, T.; Sessler, D. I.
Anaesthesia. 2015: pp. 429-33.
ABSTRACT: We measured the effect of Patent Blue dye on oxyhaemoglobin saturations after injection into breast tissue: 40 women had anaesthesia for breast surgery maintained with sevoflurane or propofol (20 randomly allocated to each). Saturations were recorded with a digital pulse oximeter, in arterial blood samples and with a cerebral tissue oximeter before dye injection and 10, 20, 30, 40, 50, 60, 75, 90, 105 and 120 min afterwards. Patent Blue did not decrease arterial blood oxyhaemoglobin saturation, but it did reduce mean (SD) digital and cerebral oxyhaemoglobin saturations by 1.1 (1.1) % and 6.8 (7.0) %, p < 0.0001 for both. The falsely reduced oximeter readings persisted for at least 2 h. The mean (SD) intra-operative digital pulse oxyhaemoglobin readings were lower with sevoflurane than propofol, 97.8 (1.2) % and 98.8 (1.0) %, respectively, p < 0.0001.

Ikemoto, K.; Ishiyama, T.; Shintani, N.; Asano, N.; Sessler, D. I.; Matsukawa, T.
BMC Anesthesiol. 2015: pp. 37.
ABSTRACT: BACKGROUND: JM-1232(-) is a novel anesthetic agent which acts through gamma-aminobutyric acid receptors. Cerebral pial vascular effects of JM-1232(-) are unknown. We thus evaluated topical and intravenous effects of JM-1232(-) on cerebral pial microvessels in rabbits, and the extent to which carbon dioxide (CO2) reactivity is preserved. METHODS: Closed cranial windows were used to visualize cerebral pial circulation in 29 Japanese white rabbits. In the first experiment, the cranial window was superfused with increasing concentrations of JM-1232(-): 10(-11), 10(-9), 10(-7), 10(-5) mol/L, n = 8 per concentration. In the second experiment, we examined the effects of an intravenous bolus of 1 mg/kg bolus of JM-1232(-), followed by the continuous infusion at 0.3 mg/kg/minute on cerebral pial vascular alteration (n = 9). In the third, we examined CO2 reactivity of cerebral pial vessels under JM-1232(-) (n = 6) or sevoflurane anesthesia (n = 6). RESULTS: Topical application of JM-1232(-) did not change pial venular diameter, and constricted arterials only at the highest concentration. Intravenous administration of JM-1232(-) produced cerebral pial constriction which gradually diminished over time. Under intravenous administration of JM-1232(-) and inhaled sevoflurane, diameters of vessels increased in parallel with CO2 partial pressure. Slopes of linear regression and correlation coefficients in arterioles and venules were comparable for JM-1232(-) anesthesia and sevoflurane anesthesia. CONCLUSIONS: Topical application of JM-1232(-) had little effect on cerebral pial vessels. Intravenous administration produced vasoconstriction of cerebral pial arterioles and venules, however those changes were clinically unimportant. In addition, JM-1232(-) did not impair CO2 responsiveness. At least from the perspective of vascular reactivity, JM-1232(-) thus appears safe for neurosurgical patients.

Bergese, S. D.; Candiotti, K.; Ayad, S. S.; Soghomonyan, S.; Gan, T. J.; Intravenous Ibuprofen Surveillance Trial Investigational, Sites
Clin Ther. 2015: pp. 360-7.
ABSTRACT: PURPOSE: The main purpose of the study was to determine the safety profile and efficacy of intravenous ibuprofen administered over 5 to 10 minutes for the treatment of pain or fever in hospitalized patients. Current evidence supports the use of intravenous infusions of ibuprofen to control pain and reduce the opioid requirements associated with surgical pain. Current dosing guidelines recommend that the drug be administered over 30 minutes. However, a more rapid infusion might yield additional benefits. The safety profile and efficacy of a shortened infusion time requires additional study. METHODS: This was a Phase IV multicenter, open-label, surveillance clinical study. Thirteen clinical centers located in the United States enrolled a total of 150 adult hospitalized patients with pain or fever. Patients experiencing pain received 800 mg intravenous ibuprofen infused over 5 to 10 minutes every 6 hours for up to 24 hours (4 doses) and patients experiencing fever received 400 mg intravenous ibuprofen infused over 5 to 10 minutes every 4 hours for up to 24 hours (6 doses). Vital signs, adverse events, and pain scores were assessed. The exclusion criteria included inadequate intravenous access; patients younger than 18 years of age; history of allergy or hypersensitivity to any component of intravenous ibuprofen, aspirin, or other nonsteroid anti-inflammatory drugs; active hemorrhage or clinically significant bleeding; pregnancy or nursing; and patients in the perioperative period in the setting of coronary artery bypass graft surgery. FINDINGS: Adverse events were reported for 43 of 150 patients (29%). The most common adverse events experienced by patients were infusion site pain in 22 of 150 patients (15%) and flatulence (8 of 150 [5%]). Four patients (3%) discontinued the study drug due to infusion-site pain. In the patients experiencing fever, temperature decreased from baseline over 4 hours (mean [SD] reduction of 1.5 [1.25] degrees F). In patients experiencing pain, patient-reported visual analog scale scores decreased from baseline over 4 hours (mean [SD] reduction of 27.1 [31.29] mm). IMPLICATIONS: The study demonstrates that more rapid administration of intravenous ibuprofen is well tolerated and supports intravenous ibuprofen as an effective treatment for pain and fever in hospitalized patients.

Gan, T. J.; Candiotti, K.; Turan, A.; Buvanendran, A.; Philip, B. K.; Viscusi, E. R.; Soghomonyan, S.; Bergese, S. D.; Intravenous Ibuprofen Surgical Surveillance Trial Investigational, Sites
Clin Ther. 2015: pp. 368-75.
ABSTRACT: PURPOSE: The literature and clinical data support the use of intravenous (IV) infusions of ibuprofen to control pain and reduce the opioid requirements associated with surgical pain. According to current guidelines, IV ibuprofen can be administered via a slow IV infusion performed during a 30-minute period. Although recent studies indicate that more rapid infusions may yield additional benefits for patients, the safety of such an approach needs further evaluation. The main purpose of this study was to determine the safety of single and multiple doses of IV ibuprofen (800 mg) administered over 5 to 10 minutes at the induction of anesthesia and after the surgical procedure for the treatment of postoperative pain. METHODS: This was a Phase IV, multicenter, open-label, clinical surveillance study. It was conducted at 21 hospitals in the United States, and 300 adult hospitalized patients undergoing surgery were enrolled. The exclusion criteria for the study were: inadequate IV access; hypersensitivity to any component of IV ibuprofen, aspirin, or related products; and any active, clinically significant bleeding. Also excluded were patients who had taken NSAIDs <6 hours before administration of IV ibuprofen; pregnant or breastfeeding female patients; and patients in the perioperative period of coronary artery bypass graft surgery. Patients received 800 mg of IV ibuprofen administered over 5 to 10 minutes preoperatively. Vital signs, adverse events, and pain scores were assessed. FINDINGS: Approximately 22% (65 of 300) of patients reported adverse events (serious and nonserious). The most common adverse event was infusion site pain (34 of 300 [11%]). No deaths were reported. Nine subjects reported serious adverse events, 8 of which occurred during the first 6 hours. All serious events reported were judged unrelated to ibuprofen. Of the 300 total patients, 2 (0.67%) discontinued the study drug due to an adverse event (1 patient discontinued the study because of infusion site pain, and 1 patient withdrew due to a hypersensitivity reaction after drug administration). IMPLICATIONS: Our study found that IV ibuprofen infused over 5 to 10 minutes at induction of anesthesia is a safe administration option for surgical patients. ClinicalTrials.gov identifier: NCT01334957.

Simmers, D.; Potgieter, D.; Ryan, L.; Fahrner, R.; Rodseth, R. N.
J Cardiothorac Vasc Anesth. 2015: pp. 389-95.
ABSTRACT: OBJECTIVE: To determine whether elevated preoperative B-type natriuretic peptide (NP) measurements are an independent predictor of atrial fibrillation (AF) in patients having thoracic surgery. DESIGN: Systematic review and meta-analysis. SETTING: In-hospital and 30 days after thoracic surgery. PARTICIPANTS: The 742 patients who participated in the 5 observational studies. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: EMBASE, OVID Health Star, Ovid Medline, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and ProQuest Dissertations and Theses A&I databases were searched for all studies of noncardiac thoracic surgery patients in whom a preoperative NP was measured up to 1 month before surgery, and that measured the incidence of postoperative AF. Studies were included regardless of their language, sample size, publication status, or study design. Study quality was evaluated using the Newcastle Ottowa Scale. The combined incidence of postoperative AF was 14.5% (n=108/742), and the NP thresholds used to predict AF varied among studies. An elevated preoperative NP measurement was associated with an OR of 3.13 (95% CI 1.38-7.12; I2=87%) for postoperative AF, with the sensitivity analysis reporting an OR of 9.51 (95% CI 4.66-19.40; I2=0). CONCLUSION: Patients with an elevated preoperative NP measurement are at an increased risk of postoperative AF. There may be value in incorporating NP measurement into existing AF risk prediction models.

Wu, J.; Buggy, D.; Fleischmann, E.; Parra-Sanchez, I.; Treschan, T.; Kurz, A.; Mascha, E. J.; Sessler, D. I.
Can J Anaesth. 2015: pp. 241-251.
ABSTRACT: BACKGROUND: The contribution of regional anesthesia with thoracic paravertebral blockade to postoperative analgesia remains unclear. We compared the effect of a combination of paravertebral blockade and propofol general anesthesia (GA) with sevoflurane GA and opioid analgesia on postoperative pain and opioid use for patients undergoing breast cancer surgery. METHODS: Patients having breast cancer surgery were randomly assigned to paravertebral analgesia with propofol GA (PPA, n = 187) or sevoflurane GA with perioperative opioid analgesia (SOA, n = 199). The PPA and SOA groups were compared for opioid consumption and pain outcomes (on a 0-10 visual analogue scale [VAS]) at two hours postoperatively using superiority and inferiority statistics. We compared our results with previous publications in a meta-analysis. RESULTS: Compared with the SOA group, the PPA group experienced reduced median [interquartile range] pain VAS scores (1 [1,3] vs 2.5 [1,4], respectively; median difference -1.0; 99% confidence intervals [CI]: -1.5 to -0.5) and required less intraoperative fentanyl (50 [0, 125] microg vs 200 [100, 300] microg, respectively; median difference -100; 99% CI: -150 to -100) and less long-acting opioid (0 [0, 0] mg vs 3.0 [0, 12] mg, respectively, morphine equivalents; median difference -3; 99% CI: -4 to -2). Thus, non-inferiority was detected for all the above outcomes, and superiority tests for each outcome were highly significant in the expected directions (P < 0.001). Meta-analysis, including the current study, estimated a reduction in worst pain of 2.3 points (95% CI: 1.8 to 2.8) on a 0-10 scale and a 72% reduction (95% CI: 42 to 87) in mean opioid consumption in the immediate two postoperative hours for PPA vs SOA. CONCLUSION: Our results were largely consistent with previous much smaller studies. Compared with sevoflurane GA with opioid analgesia, the combination of paravertebral analgesia with propofol GA provides an early clinical analgesic benefit in females having breast cancer surgery. This analysis is a substudy of an ongoing multicentre double-blinded randomized trial ( www.clinicaltrials.gov , NCT00418457) of cancer recurrence.

Nakayama, Y.; Nakajima, Y.; Tanaka, K. A.; Sessler, D. I.; Maeda, S.; Iida, J.; Ogawa, S.; Mizobe, T.
Br J Anaesth. 2015: pp. 91-102.
ABSTRACT: BACKGROUND: Thromboelastometric evaluation of coagulation might be useful for prediction and management of bleeding after paediatric cardiac surgery. We tested the hypothesis that the use of a thromboelastometry-guided algorithm for blood product management reduces blood loss and transfusion requirements. METHODS: We studied 78 patients undergoing paediatric cardiac surgery with cardiopulmonary bypass (CPB) for the initial 12 h after operation. Stepwise multiple linear regression was used to develop an algorithm to guide blood product transfusions. Thereafter, we randomly assigned 100 patients to conventional or algorithm-guided blood product management, and assessed bleeding and red cell transfusion requirements. RESULTS: CPB time, post-bypass rotational thromboelastometry (ROTEM((R))) EXTEM amplitude at 10 min (A10), and FIBTEM-A10 were independently associated with chest tube drainage volume during the initial 12 h after operation. Discriminative analysis determined cut-off values of 30 mm for EXTEM-A10 and 5 mm for FIBTEM-A10, and estimated optimal intraoperative fresh-frozen plasma and platelet concentrate transfusion volumes. Thromboelastometry-guided post-bypass blood product management significantly reduced postoperative bleeding (9 vs 16 ml kg(-1), P<0.001) and packed red cell transfusion requirement (11 vs 23 ml kg(-1), P=0.005) at 12 h after surgery, and duration of critical care stay (60 vs 71 h, P=0.014). CONCLUSIONS: Rotational thromboelastometry-guided early haemostatic intervention by rapid intraoperative correction of EXTEM-A10 and FIBTEM-A10 reduced blood loss and red cell transfusion requirements after CPB, and reduced critical care duration in paediatric cardiac surgical patients. CLINICAL TRIAL REGISTRATION: UMIN Clinical Trials Registry UMIN000006832 (December 4, 2011).

Fink, T.; Wolf, A.; Maurer, F.; Albrecht, F. W.; Heim, N.; Wolf, B.; Hauschild, A. C.; Bodeker, B.; Baumbach, J.; Volk, T.; Sessler, D. I.; Kreuer, S.
Volatile organic compounds during inflammation and sepsis in rats [no abstract available]
Anesthesiology. 2015: pp. 117-26.

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