Toby N. Weingarten

Smoking and pain: pathophysiology and clinical implications.

Cigarette smoke, which serves as a nicotine delivery vehicle in humans, produces profound changes in physiology. Experimental studies suggest that nicotine has analgesic properties. However, epidemiologic evidence shows that smoking is a risk factor for chronic pain. The complex relationship between smoking and pain not only is of scientific interest, but also has clinical relevance in the practice of anesthesiology and pain medicine. This review will examine current knowledge regarding how acute and chronic exposure to nicotine and cigarette smoke affects acute and chronic painful conditions. It will cover the relevant pharmacology of nicotine and other ligands at the nicotinic acetylcholine receptor as related to pain, explore the association of cigarette smoking with chronic painful conditions and potential mechanisms to explain this association, and examine clinical implications for the care of smokers with pain.

Protective versus Conventional Ventilation for Surgery: A Systematic Review and Individual Patient Data Meta-analysis.

Background:Recent studies show that intraoperative mechanical ventilation using low tidal volumes (VT) can prevent postoperative pulmonary complications (PPCs). The aim of this individual patient data meta-analysis is to evaluate the individual associations between VT size and positive end–expiratory pressure (PEEP) level and occurrence of PPC. Methods:Randomized controlled trials comparing protective ventilation (low VT with or without high levels of PEEP) and conventional ventilation (high VT with low PEEP) in patients undergoing general surgery. The primary outcome was development of PPC. Predefined prognostic factors were tested using multivariate logistic regression. Results:Fifteen randomized controlled trials were included (2,127 patients). There were 97 cases of PPC in 1,118 patients (8.7%) assigned to protective ventilation and 148 cases in 1,009 patients (14.7%) assigned to conventional ventilation (adjusted relative risk, 0.64; 95% CI, 0.46 to 0.88; P < 0.01). There were 85 cases of PPC in 957 patients (8.9%) assigned to ventilation with low VT and high PEEP levels and 63 cases in 525 patients (12%) assigned to ventilation with low VT and low PEEP levels (adjusted relative risk, 0.93; 95% CI, 0.64 to 1.37; P = 0.72). A dose–response relationship was found between the appearance of PPC and VT size (R2 = 0.39) but not between the appearance of PPC and PEEP level (R2 = 0.08). Conclusions:These data support the beneficial effects of ventilation with use of low VT in patients undergoing surgery. Further trials are necessary to define the role of intraoperative higher PEEP to prevent PPC during nonopen abdominal surgery.

Association between driving pressure and development of postoperative pulmonary complications in patients undergoing mechanical ventilation for general anaesthesia: a meta-analysis of individual patient data.

BACKGROUND Protective mechanical ventilation strategies using low tidal volume or high levels of positive end-expiratory pressure (PEEP) improve outcomes for patients who have had surgery. The role of the driving pressure, which is the difference between the plateau pressure and the level of positive end-expiratory pressure is not known. We investigated the association of tidal volume, the level of PEEP, and driving pressure during intraoperative ventilation with the development of postoperative pulmonary complications. METHODS We did a meta-analysis of individual patient data from randomised controlled trials of protective ventilation during general anesthaesia for surgery published up to July 30, 2015. The main outcome was development of postoperative pulmonary complications (postoperative lung injury, pulmonary infection, or barotrauma). FINDINGS We included data from 17 randomised controlled trials, including 2250 patients. Multivariate analysis suggested that driving pressure was associated with the development of postoperative pulmonary complications (odds ratio [OR] for one unit increase of driving pressure 1·16, 95% CI 1·13-1·19; p<0·0001), whereas we detected no association for tidal volume (1·05, 0·98-1·13; p=0·179). PEEP did not have a large enough effect in univariate analysis to warrant inclusion in the multivariate analysis. In a mediator analysis, driving pressure was the only significant mediator of the effects of protective ventilation on development of pulmonary complications (p=0·027). In two studies that compared low with high PEEP during low tidal volume ventilation, an increase in the level of PEEP that resulted in an increase in driving pressure was associated with more postoperative pulmonary complications (OR 3·11, 95% CI 1·39-6·96; p=0·006). INTERPRETATION In patients having surgery, intraoperative high driving pressure and changes in the level of PEEP that result in an increase of driving pressure are associated with more postoperative pulmonary complications. However, a randomised controlled trial comparing ventilation based on driving pressure with usual care is needed to confirm these findings. FUNDING None.

Comparison of two preoperative medical management strategies for laparoscopic resection of pheochromocytoma

OBJECTIVES To compare the intraoperative and postoperative course of patients undergoing laparoscopic pheochromocytoma resection at 2 institutions (Mayo Clinic and Cleveland Clinic) with differing approaches to preoperative preparation. Patients undergoing adrenalectomy for pheochromocytoma typically undergo a preoperative preparation to normalize their blood pressure and intravascular volume. However, no consensus has been reached regarding the best preoperative preparation regimen. METHODS A retrospective chart review was performed of 50 Mayo Clinic patients and 37 Cleveland Clinic patients who had undergone laparoscopic pheochromocytoma resection. Mayo Clinic predominantly used the long-lasting nonselective alpha(1,2) antagonist phenoxybenzamine, and Cleveland Clinic predominately used selective alpha(1) blockade. Data regarding the intraoperative hemodynamics and postoperative complications were collected. RESULTS Almost all patients at Mayo Clinic received phenoxybenzamine (98%). At Cleveland Clinic, the predominant treatment (65%) was selective alpha(1) blockade (doxazosin, terazosin, or prazosin). Intraoperatively, patients at Cleveland Clinic had a greater maximal systolic blood pressure (209 +/- 44 mm Hg versus 187 +/- 30 mm Hg, P = .011) and had received a greater amount of intravenous crystalloid (median 5000, interquartile range 3400-6400, versus median 2977, interquartile range 2000-3139; P <.010) and colloid (median 1000, interquartile range 500-1000, versus median 0, interquartile range 0-0; P <.001). At Mayo Clinic, more patients had received phenylephrine (56.0% versus 27.0%, P = .009). No differences were found in the postoperative surgical outcomes, and the hospital stay was comparable between the 2 groups. CONCLUSIONS Differences in the preoperative preparation and intraoperative management were associated with differences in intraoperative hemodynamics but not with clinically significant outcomes in patients undergoing laparoscopic adrenalectomy for pheochromocytoma at 2 large tertiary care centers.

Allergic reactions during anesthesia at a large United States referral center.

BACKGROUND: The types of agents implicated to trigger intraoperative anaphylactic reactions vary among reports, and there are no recent series from the United States. In this retrospective study, we examined perioperative anaphylactic reactions that occurred at a major tertiary referral academic center. METHODS: To characterize perioperative allergens associated with anaphylactic reactions, we reviewed the Mayo Clinic Division of Allergic Diseases skin test database between 1992 to 2010. The records of all patients who were tested for perioperative and anesthetic medications were reviewed. Charts that included a detailed history obtained by an allergist, skin test results, and tryptase measurements when available were reviewed and categorized. RESULTS: Thirty-eight patients were found to have an anaphylactic reaction during anesthesia, of which 18 were immunoglobulin (Ig)E-mediated anaphylactic reactions (likely causative agent identified by skin test), 6 were non–IgE-mediated anaphylactic reactions (elevated tryptase levels and negative skin test), and 14 were probable non–IgE-mediated anaphylactic reactions (tryptase levels normal or not obtained and negative skin test). Of the IgE-mediated anaphylactic reactions, antibiotics were the most prevalent likely causative agent (50%) whereas neuromuscular blocking drugs were implicated as a likely causative agent in 11% of reactions. CONCLUSION: Antibiotics were the most common likely causative agent associated with IgE-mediated anaphylactic reactions; however, for 52.6% of reactions, a causative agent could not be determined, suggesting a non–IgE-mediated anaphylactic reaction. The undiagnosed allergic reactions place patients at risk of a subsequent reexposure to the same allergen, or lead to unnecessary avoidance of needed medications.

Preoperative Gabapentin for Acute Post-thoracotomy Analgesia: A Randomized, Double-Blinded, Active Placebo-Controlled Study

Background:  The role of preoperative gabapentin in postoperative pain management is not clear, particularly in patients receiving regional blockade. Patients undergoing thoracotomy benefit from epidural analgesia but still may experience significant postoperative pain. We examined the effect of preoperative gabapentin in thoracotomy patients.

Impact of tobacco use in patients presenting to a multidisciplinary outpatient treatment program for fibromyalgia.

Objectives This study examined the relationship between the severity of fibromyalgia symptoms and current tobacco use in patients evaluated at a specialized fibromyalgia treatment program. Methods Demographic and clinical data from 984 consecutive patients evaluated at the Mayo Clinic Fibromyalgia Treatment Program including the Fibromyalgia Impact Questionnaire (FIQ) were prospectively collected and stored in an electronic medical record and an electronic database. Univariate analyses were performed comparing tobacco users and nonusers. A post-hoc analysis of covariance was conducted for tobacco use, using group differences of confounding clinical and demographic variables. A P value ≤ 0.05 was accepted as the level of significance. Results One hundred and forty-five patients were identified as tobacco users (14.7%). Tobacco use was associated with greater pain intensity as measured by pain scales and the pain component of the FIQ. Tobacco users had a greater FIQ composite score 70.0(15.1) versus 61.8(16.8), P<0.001. By univariate analysis, tobacco users had higher scores on all the FIQ components and fewer good days and more days of work missed per week. Tobacco use was associated with several confounding clinical and demographic variables including lower education, higher unemployment, not being married or widowed, and history of abuse. After adjusting for these confounding variables, tobacco users continued to have greater pain intensity, a higher total and component FIQ scores except for fatigue. Smoking was not associated with a higher number of tender points. Discussion Current tobacco use was associated with more severe fibromyalgia symptoms in patients presenting to a specialized fibromyalgia treatment program.

Validation of the S-LANSS in the community setting☆

Abstract The Self‐Administered Leeds Assessment of Neuropathic Symptoms and Signs (S‐LANSS), an assessment tool to determine if pain is predominantly neuropathic, has not been validated in a community setting. Previously identified residents of Olmsted County, Minnesota, with chronic pain were recruited using a stratified randomization process to increase the frequency of neuropathic pain in the study sample. Subjects completed the S‐LANSS in mailed and telephone formats, and underwent clinical assessment to determine if a component of their pain was neuropathic. Sensitivity and specificity of the S‐LANSS as compared to the clinical assessment were determined. Two hundred and five subjects participated in the study. Eighty‐three subjects (40%) had a positive S‐LANSS score in the mailed, as did 59 of 173 (34%) in the telephone format, with little inter‐subject difference in scores (p = 0.57). Clinical assessment identified a component of neuropathic pain in 37% of the sample (75/205). Compared to clinical assessment, sensitivity and specificity in the mailed S‐LANSS were 57% (95% CI, 46–69%) and 69% (95% CI, 61–77%), respectively, and in the telephone S‐LANSS were 52% (95% CI, 39–64%) and 78% (95% CI, 68–85%), respectively. The sensitivity and specificity of the S‐LANSS in both formats were lower than the initial S‐LANSS validation study. Differences in survey format and subject population could account for these differences, suggesting that the S‐LANSS is best suited as a screening tool and its use to determine the prevalence of neuropathic pain in population studies should be viewed cautiously.

Anesthesia and Incident Dementia: A Population-Based Nested Case-Control Study

OBJECTIVE To test the hypothesis that exposure to procedures requiring general anesthesia during adulthood is not significantly associated with incident dementia using a retrospective, population-based, nested, case-control study design. PARTICIPANTS AND METHODS Using the Rochester Epidemiology Project and the Mayo Clinic Alzheimers Disease Patient Registry, residents of Olmsted County, Minnesota, diagnosed as having dementia between January 1, 1985, and December 31, 1994, were identified. For each incident case, a sex- and age-matched control was randomly selected from the general pool of Olmsted County residents who were dementia free in the index year of dementia diagnosis. Medical records were reviewed to determine exposures to procedures requiring anesthesia after age 45 years and before the index year. Data were analyzed using logistic regression. RESULTS We analyzed 877 cases of dementia, each with a corresponding control. Of the dementia cases, 615 (70%) underwent 1681 procedures requiring general anesthesia; of the controls, 636 (73%) underwent 1638 procedures. When assessed as a dichotomous variable, anesthetic exposure was not significantly associated with dementia (odds ratio, 0.89; 95% CI, 0.73-1.10; P=.27). In addition, no significant association was found when exposure was quantified as number of procedures (odds ratios, 0.87, 0.86, and 1.0 for 1, 2-3, and ≥4 exposures, respectively, compared with none; P=.51). CONCLUSION This study found no significant association between exposure to procedures requiring general anesthesia after age 45 years and incident dementia.

Intraoperative management of patients with carcinoid heart disease having valvular surgery : A review of one hundred consecutive cases

BACKGROUND:Cardiac surgery for carcinoid heart disease is complicated by hemodynamic instability secondary to carcinoid crises, cardiovascular dysfunction, and blood loss. The safety of vasopressors and the benefit of aprotinin during concomitant octreotide administration are uncertain. METHODS:We reviewed the effects of vasopressors and aprotinin on octreotide administration and mortality by univariate analysis in 100 consecutive cases of cardiac surgery for carcinoid heart disease from 1985 to 2003. Because mortality declines were temporally related to the introduction of aprotinin, bivariate analyses were performed to identify other factors associated with mortality. RESULTS:Carcinoid symptoms and hypotension were treated with octreotide (n = 89) and/or vasopressors (n = 93). Vasopressors were not associated with increased octreotide administration. Patients requiring epinephrine had higher mortality but also had worse preoperative New York Heart Association class, higher urinary 5-hydroxyindoleacetic acid levels, and increased blood transfusion requirements. Aprotinin (n = 54) was associated with decreased blood transfusion requirements, increased octreotide administration, but not mortality. Overall mortality was 13%, declining from 28% between 1985 and 1994 to 6% between 1995 and 2003. Mortality was associated with greater blood transfusion requirements and longer duration of cardiopulmonary bypass. CONCLUSIONS:Vasopressors may be used in conjunction with octreotide in carcinoid patients. The increased mortality associated with epinephrine likely reflects selection bias rather than a primary adverse effect. The improved survival over time in carcinoid patients is multifactorial and unrelated to aprotinin administration, suggesting further inhibition of the kallikrein–kinin system has little added benefit for this outcome in the presence of octreotide.