Kenneth C. Cummings

Liposomal bupivacaine: a review of a new bupivacaine formulation

Many attempts have been made to increase the duration of local anesthetic action. One avenue of investigation has focused on encapsulating local anesthetics within carrier molecules to increase their residence time at the site of action. This article aims to review the literature surrounding the recently approved formulation of bupivacaine, which consists of bupivacaine loaded in multivesicular liposomes. This preparation increases the duration of local anesthetic action by slow release from the liposome and delays the peak plasma concentration when compared to plain bupivacaine administration. Liposomal bupivacaine has been approved by the US Food and Drug Administration for local infiltration for pain relief after bunionectomy and hemorrhoidectomy. Studies have shown it to be an effective tool for postoperative pain relief with opioid sparing effects and it has also been found to have an acceptable adverse effect profile. Its kinetics are favorable even in patients with moderate hepatic impairment, and it has been found not to delay wound healing after orthopedic surgery. More studies are needed to establish its safety and efficacy for use via intrathecal, epidural, or perineural routes. In conclusion, liposomal bupivacaine is effective for treating postoperative pain when used via local infiltration when compared to placebo with a prolonged duration of action, predictable kinetics, and an acceptable side effect profile. However, more adequately powered trials are needed to establish its superiority over plain bupivacaine.

A comparison of epidural analgesia and traditional pain management effects on survival and cancer recurrence after colectomy: a population-based study.

Background: Cancer recurrence after surgery may be affected by immunosuppressive factors such as surgical stress, anesthetic drugs, and opioids. By limiting exposure to these, epidural analgesia may enhance tumor surveillance. This study compared survival and cancer recurrence rates for resection of colorectal cancer between patients who received perioperative epidurals and those who did not. Methods: The linked Medicare-Surveillance, Epidemiology, and End Results database was used to identify patients ages 66 yr or older with nonmetastatic colorectal cancer diagnosed between 1996 and 2005 who underwent open colectomy. Recurrence was defined as chemotherapy 16 months or more after surgery and/or radiation 12 months or more after surgery. Patients were followed for at least 4 yr. To account for hospital effects, overall survival was estimated via marginal Cox regression. Recurrence was estimated by conditional logistic regression. Results: A cohort of 42,151 patients, of whom 22.9% (n = 9,670) had epidurals at the time of resection, was identified. 5-yr survival was 61% in the epidural group and 55% in the nonepidural group. There was a significant association between epidural use and improved survival (adjusted Cox model hazard ratio = 0.91, 95% CI = [0.87, 0.94]). Adjusting for covariates, there was no significant reduction of recurrence in the epidural group (odds ratio = 1.05, 95% CI = [0.95, 1.15]). Several covariates, including blood transfusion, were predictive of mortality and cancer recurrence. Conclusion: This large cohort study found that epidural use is associated with improved survival in patients with nonmetastatic colorectal cancer undergoing resection but does not support an association between epidural use and decreased cancer recurrence.

Case report: Fentanyl-associated intraoperative anaphylaxis with pulmonary edema

PurposeTo describe an atypical presentation of intraoperative anaphylaxis due to fentanyl.Clinical featuresA 40-yr-old otherwise healthy woman was admitted for abdominal hysterectomy. She denied any drug allergies or past adverse anesthetic reactions. Physical examination, vital signs, and laboratory findings were all within normal limits. Twenty minutes after induction of general anesthesia with propofol, lidocaine, fentanyl, and rocuronium, she developed sudden onset of hypotension and bronchospasm. She was treated with fluids and epinephrine, but nonetheless required mechanical ventilation for 48 hr. Chest x-ray revealed pulmonary edema which resolved over two days. She recovered completely and was discharged home. Subsequent skin testing showed reactions to fentanyl and succinylcholine. Because the patient had not received succinylcholine, the cause of her anaphylaxis was attributed to fentanyl. The patient later returned for her hysterectomy and tolerated spinal anesthesia with bupivacaine and morphine.ConclusionAnaphylaxis is a fulminant, unexpected, IgE-mediated allergic reaction which can be triggered by multiple agents. Common causative agents include neuromuscular blocking drugs, latex, antibiotics, colloids, hypnotics, and opioids. Fentanyl, however, is an extremely unusual cause of anaphylaxis. Pulmonary edema, although uncommon in anaphylaxis, can be a prominent feature, as was the case with this patient.RésuméObjectifDécrire la présentation atypique d’anaphylaxie peropératoire due au fentanyl.Éléments cliniquesUne femme de 40 ans en bonne santé a été admise pour une hystérectomie abdominale. Elle ne se connaissait pas d’allergie aux médicaments ou avoir eu de réactions adverses à l’anesthésie par le passé. L’examen physique, les signes vitaux et les tests de laboratoire ont tous présenté des résultats normaux. Elle a soudainement développé de l’hypotension ainsi qu’un bronchospasme vingt minutes après l’induction de l’anesthésie générale avec propofol, lidocaïne, fentanyl et rocuronium. On lui a administré des liquides et de l’épinéphrine, mais elle a tout de même eu besoin de ventilation mécanique durant 48 h. Une radiographie des poumons a révélé un œdème pulmonaire qui s’est résorbé en deux jours. Elle s’est complètement rétablie et a pu rentrer à la maison. Des tests cutanés ultérieurs ont montré des réactions au fentanyl et au suxaméthonium. Puisque la patiente n’avait pas reçu de suxaméthonium, le fentanyl a été tenu responsable de son anaphylaxie. La patiente est revenue plus tard pour son hystérectomie et a toléré la rachianesthésie avec de la bupivacaïne et de la morphine.ConclusionL’anaphylaxie est une réaction allergique fulminante, inattendue, médiée par les IgE, qui peut être provoquée par de nombreux agents. Les bloqueurs neuromusculaires, le latex, les antibiotiques, les colloïdes, les hypnotiques et les opiacés sont tous des agents connus pour leur potentiel anaphylactique. Cependant, il est très inhabituel que le fentanyl cause l’anaphylaxie. L’œdème pulmonaire, bien que peu répandu lors d’une réaction anaphylactique, peut devenir un trait proéminent, comme dans le cas décrit ici.

A comparison of the effects of epidural analgesia versus traditional pain management on outcomes after gastric cancer resection: A population-based study

Background and Objectives Epidural analgesia may increase survival after cancer surgery by reducing recurrence. This population-based study compared survival and treated recurrence after gastric cancer resection between patients receiving epidurals and those who did not. Methods We used the linked federal Surveillance, Epidemiology, and End Results Program/Medicare database to identify patients aged 66 years or older with nonmetastatic gastric carcinoma diagnosed 1996 to 2005 who underwent resection. Exclusions included diagnosis at autopsy, no Medicare Part B, familial cancer syndrome, emergency surgery, and laparoscopic procedures. Epidurals were identified by Current Procedural Terminology codes. Treated recurrence was defined as chemotherapy greater than or equal to 16 months and/or radiation greater than or equal to 12 months after surgery. Recurrence was compared by conditional logistic regression. Survival was compared via marginal Cox proportional hazards regression model. Results We identified 2745 patients, 766 of whom had epidural codes. Patients receiving epidurals were more likely to have regional disease, be white, and live in areas with relatively high socioeconomic status. Overall treated recurrence was 25.6% (27.5% epidural and 24.9% nonepidural). In the adjusted logistic regression, there was no difference in recurrence (odds ratio, 1.40; 95% confidence interval [CI], 0.96–2.05). Median survival did not differ: 28.1 months (95% CI, 24.8–32.3) in the epidural versus 27.4 months (95% CI, 24.8–30.0) in the nonepidural groups. The marginal Cox models showed no association between epidural use and mortality (adjusted hazard ratio, 0.93; 95% CI, 0.84–1.03). Conclusions There was no difference between groups regarding treated recurrence or survival. Whether this is true or simply a result of insufficient power is unclear. Prospective studies are needed to provide stronger evidence.

Absence of proof is not proof of absence.

To the Editor: W e read with great interest the recent article by Wongyingsinn et al describing a comparison between the effects of intravenous lidocaine and thoracic epidural anesthesia on the return of bowel function after surgery. They are to be congratulated on an elegant and relevant clinical trial. We believe, however, that their statistical analysis is not congruent with their hypothesis. In the introduction, they state ‘‘It is hypothesized that intraoperative and postoperative lidocaine would result in postoperative restoration of bowel function similar to TEA in patients undergoing laparoscopic colorectal resection when an ERP was implemented.’’ Their hypothesis is thus one of equivalence, namely that 2 regimens are similar. Their sample size estimates and comparisons between groups are based on testing for superiority. They designed the study to have 80% power at the 0.05 significance level to detect a difference of 16 hours (with SD of 19 and 20 per group) in time to return of bowel function between regimens, for which 50 total patients were required. In their analysis, they failed to find a statistically significant difference and therefore concluded that the regimens lead to a similar outcome. Based on their methods, however, the authors can only assert that no difference in outcome was detected, not that no difference exists. As one of us has previously noted, a more correct approach would be to use an equivalence or noninferiority design. An equivalence trial depends on an a priori definition of ‘‘equivalence,’’ that is, the range of differences within which the groups are considered to be clinically the same. Study design and statistical testing thus aim to determine whether the true difference actually falls within this ‘‘equivalence’’ region. If the investigator wanted to determine that a new regimen is ‘‘better or not much worse than’’ the current, a noninferiority design should be used with a range of values ‘‘worse’’ than the reference group that are not clinically significantly worse. An appropriate equivalence delta should typically be smaller than the difference used to plan a superiority trial, given the goal of claiming 2 interventions are clinically the same. For the study by Wongyingsinn et al, we think a difference of more than 8 hours in time to return of bowel function would be clinically important. An appropriate equivalence design sample size for 80% power at the 0.05 significance level would require 206 total patients, much larger than planned. Furthermore, because 2 primary outcomes were analyzed (time to flatus and bowel function), and each within anastomosis and ileostomy patients, an appropriate significance level for each of the 4 tests would be 0.0125, requiring many more patients (150 per group) for each test! Applying an equivalence delta of 8 hours to the summary data in Wongyingsinn et al, 95% confidence intervals for the group differences in anastomosis patients arej10 to 4 andj11 to 13 for time to flatus and bowel function, respectively, and j18 to 12 and j16 to 22 for ileostomy patients. Thus, using a delta of 8 hours, equivalence cannot be claimed for any of the comparisons because all intervals go beyond T8 hours. If the a priori delta were 12 hours instead, equivalence would only be claimed for time to flatus in anastomosis patients. And although we think an unreasonably wide equivalence region, both anastomosis comparisons would be deemed equivalent using 16 hours, but for neither of the ileostomy comparisons. In summary, when the goal is to claim that 2 interventions are the same, as in Wongyingsinn et al, or that one is at least not worse than the other, traditional superiority designs and tests cannot be used. An appropriate equivalence or noninferiority design requires a priori specification of the equivalence region, which is used in design and analysis. In such studies, a statistically significant result is required to claim equivalence or noninferiority, thus avoiding claims of ‘‘equivalence’’ in negative and perhaps underpowered tests for superiority.

The Cleveland Clinic Experience with Supraclavicular and Popliteal Ambulatory Nerve Catheters

Continuous peripheral nerve blocks (CPNB) are commonly used for intraoperative and postoperative analgesia. Our study aimed at describing our experience with ambulatory peripheral nerve catheters. After Institutional Review Board approval, records for all patients discharged with supraclavicular or popliteal catheters between January 1, 2009 and December 31, 2011 were reviewed. A licensed practitioner provided verbal and written instructions to the patients prior to discharge. Daily follow-up phone calls were conducted. Patients either removed their catheters at home with real-time simultaneous telephone guidance by a member of the Acute Pain Service or had them removed by the surgeon during a regular office visit. The primary outcome of this analysis was the incidence of complications, categorized as pharmacologic, infectious, or other. The secondary outcome measure was the average daily pain score. Our study included a total of 1059 patients with ambulatory catheters (769 supraclavicular, 290 popliteal). The median infusion duration was 5 days for both groups. Forty-two possible complications were identified: 13 infectious, 23 pharmacologic, and 6 labeled as other. Two patients had retained catheters, 2 had catheter leakage, and 2 had shortness of breath. Our study showed that prolonged use of ambulatory catheters for a median period of 5 days did not lead to an increased incidence of complications.

Attempted Development of a Tool to Predict Anesthesia Preparation Time From Patient-Related and Procedure-Related Characteristics

BACKGROUND: Operating room (OR) utilization generally ranges from 50% to 75%. Inefficiencies can arise from various factors, including prolonged anesthesia preparation time, defined as the period from induction of anesthesia until patients are considered ready for surgery. Our goal was to use patient-related and procedure-related factors to develop a model predicting anesthesia preparation time. METHODS: From the electronic medical records of adults who had noncardiac surgery at the Cleveland Clinic Main Campus, we developed a model that used a dozen preoperative factors to predict anesthesia preparation time. The model was based on multivariable regression with “Least Absolute Shrinkage and Selection Operator” and 10-fold cross-validation. The overall performance of the final model was measured by R2, which describes the proportion of the variance in anesthesia preparation time that is explained by the model. RESULTS: A total of 43,941 cases met inclusion and exclusion criteria. Our final model had only moderate discriminative ability. The estimated adjusted R2 for prediction model was 0.34 for the training data set and 0.27 for the testing data set. CONCLUSIONS: Using preoperative factors, we could explain only about a quarter of the variance in anesthesia preparation time—an amount that is probably of limited clinical value.

Complications and Anesthesia for Colonoscopy: Culprit or Accomplice?

2 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 Dear Editor: I read with great interest the recent paper by Wernli et al and its accompanying editorial. As a practicing anesthesiologist, it is always interesting to read other specialties’ literature involving my own specialty. I believe, however, that this paper and editorial perpetuate misconceptions and look to point fingers in the wrong direction. The authors’ principal finding is that, using billing data from the MarketScan databases, colonoscopies with billing codes for anesthetic care had an increased incidence of multiple complications, including perforation and hemorrhage. Their statistical methods are generally sound and they use validated measures. The weakness in this paper and accompanying editorial, however, is relying on several assumptions. First, they assume that the presence of an anesthesia billing code equals the administration of propofol. Second, they assume that the administration of propofol, ipso facto, produces deeper sedation than commonly-used benzodiazepine/opioid regimens. The American Society of Anesthesiologists Definition of General Anesthesia and Levels of Sedation/Analgesia recognizes multiple levels of sedation during the provision of monitored anesthesia care, any of which is possible during care by an anesthesia provider. Third, they assume that the quality and type of anesthetic care given is constant, regardless of provider qualification (physician vs nurse anesthetist) and patient comorbidity. These assumptions plus a statistical association led to a logical fallacy: anesthetic care increases postprocedural complications. A more plausible explanation for their finding of an association is that the involvement of an anesthesia provider includes an expectation by the patient (or endoscopist) for deeper sedation and produces (1) a more comfortable patient and (2) an overconfident endoscopist. If a patient is not complaining of discomfort during a procedure, how does one assign responsibility for

Spectral analysis of ultrasound radiofrequency backscatter for the identification of five tissue types found in and around the paravertebral space

In a pilot study, radiofrequency backscatter data was collected in the paravertebral (PV) spaces of 4 healthy individuals. Using the associated gray scale ultrasound and Doppler data as guidance, regions-of-interest (ROIs) were chosen to represent five tissue types found in and around the PV space – rib shadow, pleura, superior costotransverse ligament, intercostal vessel (artery or vein), and the PV space away from the vessel. ROI sizes of 1.0 mm, 1.5 mm, and 2.0 mm square were examined for auto-regressive (AR) orders of 10, 20, 30, and 40 and bandwidths of 3dB, 6dB, 20dB. Spectral estimations were performed for each ROI size, AR order, and bandwidth over the A-lines of the ultrasound radiofrequency data. The spectra were averaged and normalized using data collected from a tissue phantom. Eight spectral parameters – Y-intercept, slope, and mid-band fit of the regression line, maximum dB of the spectra, frequency at maximum dB, minimum dB of the spectra, frequency at minimum dB, and integrated backscatter were calculated for each spectral estimate and used to create ensembles of bagged tree classifiers. An ROI size of 2.0 mm, bandwidth of 20 dB, and AR order 10 had the lowest out-of-bag error at 0.315, and averaged across all tissue types, an accuracy of 89.15%, sensitivity of 0.70, specificity of 0.93, and Youden’s Index (YI) of 0.62. These results show that the identification of the five tissues types in radiofrequency backscatter from intercostal ultrasound is feasible.

Endotracheal intubation and process metrics

1 Liver Center, Cathay General Hospital Medical Center , Taipei , Taiwan ; 2 School of Medicine, Taipei Medical University College of Medicine , Taipei , Taiwan ; 3 Division of Gastroenterology, Department of Internal Medicine, National Taiwan University College of Medicine , Taipei , Taiwan ; 4 School of Medicine, China Medical University , Taichung , Taiwan ; 5 School of Medicine, Fu-Jen Catholic University College of Medicine , Taipei , Taiwan . Correspondence: Yi-Wen Huang, MD, PhD, Liver Center and Health Management Center, Cathay General Hospital Medical Center , No. 280, Sec. 4, Jen-Ai Road , 10630 Taipei , Taiwan . E-mail: yiwenhuang@ntu.edu.tw