Michael P. Mangione

Association between Intraoperative Hypotension and Hypertension and 30-day Postoperative Mortality in Noncardiac Surgery.

Background:Although deviations in intraoperative blood pressure are assumed to be associated with postoperative mortality, critical blood pressure thresholds remain undefined. Therefore, the authors estimated the intraoperative thresholds of systolic blood pressure (SBP), mean blood pressure (MAP), and diastolic blood pressure (DBP) associated with increased risk-adjusted 30-day mortality. Methods:This retrospective cohort study combined intraoperative blood pressure data from six Veterans Affairs medical centers with 30-day outcomes to determine the risk-adjusted associations between intraoperative blood pressure and 30-day mortality. Deviations in blood pressure were assessed using three methods: (1) population thresholds (individual patient sum of area under threshold [AUT] or area over threshold 2 SDs from the mean of the population intraoperative blood pressure values), (2). absolute thresholds, and (3) percent change from baseline blood pressure. Results:Thirty-day mortality was associated with (1) population threshold: systolic AUT (odds ratio, 3.3; 95% CI, 2.2 to 4.8), mean AUT (2.8; 1.9 to 4.3), and diastolic AUT (2.4; 1.6 to 3.8). Approximate conversions of AUT into its separate components of pressure and time were SBP < 67 mmHg for more than 8.2 min, MAP < 49 mmHg for more than 3.9 min, DBP < 33 mmHg for more than 4.4 min. (2) Absolute threshold: SBP < 70 mmHg for more than or equal to 5 min (odds ratio, 2.9; 95% CI, 1.7 to 4.9), MAP < 49 mmHg for more than or equal to 5 min (2.4; 1.3 to 4.6), and DBP < 30 mmHg for more than or equal to 5 min (3.2; 1.8 to 5.5). (3) Percent change: MAP decreases to more than 50% from baseline for more than or equal to 5 min (2.7; 1.5 to 5.0). Intraoperative hypertension was not associated with 30-day mortality with any of these techniques. Conclusion:Intraoperative hypotension, but not hypertension, is associated with increased 30-day operative mortality.

Eliminating arterial injury during central venous catheterization using manometry.

BACKGROUND: Unintended arterial puncture occurs in 2%-4.5% of central venous catheterizations, resulting in arterial injury in 0.1%-0.5% of patients. Routine performance of manometry during catheterization may successfully identify unintended arterial puncture and avoid arterial cannulation and injury. METHODS: We conducted a retrospective review of all cases of central venous catheter placement during a 15-yr period after implementation of a safety program requiring mandatory use of manometry to verify venous access. Arterial injuries were defined as unintended arterial cannulations with a 7-French or larger catheter or dilator. Arterial punctures were defined as the unintended placement of an 18-gauge catheter or needle into the artery. Data were reviewed for all arterial injuries during the entire 15-yr period. In addition, data on both arterial puncture and subsequent arterial injury were evaluated during the final year of analysis. RESULTS: A total of 9348 central venous catheters were placed during the observation period. During the full 15 yr of observation, there were no cases of arterial injury. During the final year of assessment, 511 central venous catheters were placed, with arterial punctures in 28 patients (5%). Arterial puncture was recognized without manometry in 24 cases. Arterial puncture was identified only with manometry in 4 cases, with no incidents of arterial injury. CONCLUSIONS: Consistent use of manometry, to verify venous placement, during central venous catheterization effectively eliminated arterial injury from unintended arterial cannulation during the 15-yr assessment.

Asystole after intravenous neostigmine in a heart transplant recipient

Purpose: To describe a heart transplant recipient who developed asystole after administration of neostigmine which suggests that surgical dennervation of the heart may not permanently prevent significant responses to anti-cholinesterases.Clinical features: A 67-yr-old man, 11 yr post heart transplant underwent left upper lung lobectomy. He developed asystole after intravenous administration of 4 mg neostigmine with 0.8 mg glycopyrrolate for reversal of the muscle relaxant. He had no history of rate or rhythm abnormalities either prior to or subsequent to the event.Conclusion: When administering anticholinesterase medications to heart transplant patients, despite surgical dennervation, one must be prepared for a possible profound cardiac response.RésuméObjectif: Décrire le cas d’un receveur de greffe cardiaque qui a développé une a systole après l’administration de néostigmine, ce qui laisse croire que la dénervation cardiaque ne préviendrait pas de façon permanente des réactions signifcatives aux anticholinestérases.Éléments cliniques: Un homme de 67 ans, receveur d’une greffe cardiaque 11 ans plus tôt, a subi une lobectomie pulmonaire supérieure gauche. Il a développé une asystole après l’administration intraveineuse de 4 mg de néostigmine et de 0,8 mg de glycopyrrolate pour renverser l’effet du myorelaxant. Il n’a jamais présenté quelque anomalie de la fréquence ou du rythme cardiaque que ce soit avant ou après l’incident.Conclusion: Quand on administre une médication anticholinestérasique aux patients receveurs de greffe cardiaque, il faut être prêt, malgré une dénervation chirurgicale, à faire face à une réponse cardiaque marquée possible.

Research Priorities Regarding Multimodal Peripheral Nerve Blocks for Postoperative Analgesia and Anesthesia Based on Hospital Quality Data Extracted from Over 1,300 Cases (2011–2014)

The use of additives with local anesthetics for peripheral nerve blocks has received considerable attention [1] due to the patient-centered goals of prolonging analgesic duration and possibly reducing local anesthetic-related toxicity. Applying such additives to single-injection nerve blocks also has the potential to reduce overhead [2] and disposables [3] costs, when compared with the costs related to continuous perineural infusions. Furthermore, recent research has elucidated in vivo animal sciatic nerve safety of the preservative-free combination of clonidine, buprenorphine, and dexamethasone (CBD) with the local anesthetic bupivacaine (BPV) [4]. Ropivacaine–CBD was previously demonstrated to be no more neurotoxic than plain ropivacaine to cultured primary sensory neurons harvested from rat dorsal root ganglia in vitro [5]. In our institution (Veterans Affairs Pittsburgh Healthcare System [VAPHS]), the lead author was in charged with creating a regional anesthesia (RA) and analgesia program for patients eligible for peripheral nerve blocks. For this new program, hospital administration was unable to budget resources for a perineural catheter-based acute pain service. Instead, the Medical Executive Board approved the lead authors recommendation to routinely use BPV–CBD off-label. These single-injection nerve block procedures are typically placed before surgery to provide postoperative analgesia and intraoperative anesthesia when feasible, and thus avoiding general endotracheal anesthesia (GETA). The Medical Executive Board tasked the lead author with per-patient quality assurance/quality improvement (QA/QI) data collection to evaluate comparative effectiveness (against historical controls) and outcomes (block duration and rebound pain [6,7], perineural complications, etc.). In accordance with Veterans Health Administration Handbook 1058.05, this manuscript was processed for authentication of nonresearch status of the activities prior to submission to this journal. Our institutional review board declared these clinical operations as “not research” at the time of program initiation (mid-2011) and annually since then during required reviews. The objective is to describe the patient outcomes …

Local anesthetics in diabetic rats (and patients): shifting from a known slippery slope toward a potentially better multimodal perineural paradigm?

Despite the calls for focused research on diabetes mellitus (DM) and peripheral nerve blockade, and the resulting studies on this topic, there remain important research opportunities to explore perineural analgesia options that are less reliant upon neurotoxic (in vitro) local anesthetics. In this issue of the Regional Anesthesia and Pain Medicine, Kroin et al and Lirk et al report their investigations on the effect of hyperglycemia in 2 different rodent models of diabetes: the traditional streptozotocin (STZ)Yinduced diabetic state with peripheral neuropathy (a model more similar to type 1 or insulin-dependent DM) and the Zucker diabetic fatty (ZDF) model of type 2 DM. These studies, considered together, illustrate a ‘‘slippery slope’’ when only local anesthetics are used for peripheral nerve blocks in diabetic rodents. How this ‘‘slippery slope’’ could adversely affect our patients with subclinical diabetic neuropathy remains unknown. Using the STZ model, Kroin et al showed that (i) local anesthetic nerve block duration was prolonged in the chronic hyperglycemic state, and (ii) block duration does not depend on the presence of coinciding acute tissue hyperglycemia. Only with sustained glycemic control over time (2 weeks) was there a return of nerve block duration to the nondiabetic baseline after the use of local anesthetics. Kroin et al did not evaluate tissue toxicity in this study related to the perineural injections (having already performed elegant histological analysis in previous work), instead only reporting that there were no gait abnormalities in any of the diabetic rats after the nerve block effects dissipated. Lirk et al examined local anesthetic block duration using ZDF rats as a model of type 2 DM. As with the STZ model of Kroin et al, block duration was increased from baseline in ZDF diabetic rats with chronic hyperglycemia, even though the ZDF rats showed only subclinical neuropathy. This is an important inaugural study of local anestheticYinduced neurotoxicity in a ZDF model and represents a major step forward for clinicians who should be concerned about the long-term effect of peripheral nerve blocks with local anesthetics on DM-induced peripheral neuropathy, primarily because the ZDF rat appears to more accurately represent the most common DM clinical condition from an epidemiological standpoint. As our knowledge currently stands, the local anesthetics (eg, lidocaine, ropivacaine, etc) that are approved by the US Food and Drug Administration are notably neurotoxic in vitro. Lirk et al further illustrate this, finding that a hyperglycemic environment did not alter the toxicity of lidocaine to primary sensory neurons in culture, but that lidocaine was slightly more neurotoxic in diabetic rats. Again, the acute hyperglycemic milieu does not seem to matter; it is the neuronal changes that occur over the long term that put diabetic neurons (and nerves) at risk. In the opinion of Lirk et al, the neurotoxicity difference between treatment groups was small. However, we believe that ‘‘small’’ does not equal ‘‘clinically insignificant.’’ We acknowledge that morphologic changes in the nerve do not always correlate to function, but observing transient analgesia/anesthesia in a laboratory rodent that then resolves to ‘‘no change from baseline’’does not rule out that there was some nerve fiber degeneration, as the nervous system has considerable redundancy to ‘‘clinically’’ compensate (personal communication, M. T. Butt, DVM, ACVP, Frederick, Maryland). Evolving bench evidence of the subtle perineural deficits created by prototypical local anesthetics in the diabetic model, including the prolonged block duration and neurotoxicity described in the aforementioned studies, continues to alert our subspecialty to the need to consider other perineural mechanisms of analgesia. EDITORIAL

Intermediate-acting Nondepolarizing Neuromuscular Blocking Agents and Risk of Postoperative 30-day Morbidity and Mortality, and Long-term Survival

BACKGROUND: Nondepolarizing neuromuscular blocking drugs (NNMBDs) are commonly used as an adjunct to general anesthesia. Residual blockade is common, but its potential adverse effects are incompletely known. This study was designed to assess the association between NNMBD use with or without neostigmine reversal and postoperative morbidity and mortality. METHODS: This is a retrospective observational study of 11,355 adult patients undergoing general anesthesia for noncardiac surgery at 5 Veterans Health Administration (VA) hospitals. Of those, 8984 received NNMBDs, and 7047 received reversal with neostigmine. The primary outcome was a composite of respiratory complications (failure to wean from the ventilator, reintubation, or pneumonia), which was “yes” if a patient had any of the 3 component events and “no” if they had none. Secondary outcomes were nonrespiratory complications, 30-day and long-term all-cause mortality. We adjusted for differences in patient risk using propensity matched (PM) followed by assessment of the association of interest by logistic regression between the matched pairs as our primary analysis and multivariable logistic regression (MLR) as a sensitivity analysis. RESULTS: Our primary aim was to assess the adverse outcomes in the patients who had received NNMBDs with and without neostigmine. Administration of an NNMBD without neostigmine reversal compared with NNMBD with neostigmine reversal was associated with increased odds of respiratory complications (PM odds ratio [OR], 1.75 [95% confidence interval [CI], 1.23–2.50]; MLR OR, 1.71 [CI, 1.24–2.37]) and a marginal increase in 30-day mortality (PM OR, 1.83 [CI, 0.99–3.37]; MLR OR, 1.78 [CI, 1.02–3.13]). However, there were no statistically significant associations with nonrespiratory complications or long-term mortality. Patients who were administered an NNMBD followed by neostigmine had no differences in outcomes compared with patients who had general anesthesia without an NNMBD. CONCLUSIONS: The use of NNMBDs without neostigmine reversal was associated with increased odds of our composite respiratory outcome compared with patients reversed with neostigmine. Based on these data, we conclude that reversal of NNMBDs should become a standard practice if extubation is planned.

Endotracheal intubation skill acquisition by medical students

Abstract Background During the course of their training, medical students may receive introductory experience with advanced resuscitation skills. Endotracheal intubation (ETI – the insertion of a breathing tube into the trachea) is an example of an important advanced resuscitation intervention. Only limited data characterize clinical ETI skill acquisition by medical students. We sought to characterize medical student acquisition of ETI procedural skill.1 1Presented as a poster discussion on 17 October 2007 at the annual meeting of the American Society of Anesthesiologists in San Francisco, CA. Methods The study included third-year medical students participating in a required anesthesiology clerkship. Students performed ETI on operating room patients under the supervision of attending anesthesiologists. Students reported clinical details of each ETI effort, including patient age, sex, Mallampati score, number of direct laryngoscopies and ETI success. Using mixed-effects regression, we characterized the adjusted association between ETI success and cumulative ETI experience. Results ETI was attempted by 178 students on 1,646 patients (range 1–23 patients per student; median 9 patients per student, IQR 6–12). Overall ETI success was 75.0% (95% CI 72.9–77.1%). Adjusted for patient age, sex, Mallampati score and number of laryngoscopies, the odds of ETI success improved with cumulative ETI encounters (odds ratio 1.09 per additional ETI encounter; 95% CI 1.04–1.14). Students required at least 17 ETI encounters to achieve 90% predicted ETI success. Conclusions In this series medical student ETI proficiency was associated with cumulative clinical procedural experience. Clinical experience may provide a viable strategy for fostering medical student procedural skills.

Clinical Benchmarks Regarding Multimodal Peripheral Nerve Blocks for Postoperative Analgesia: Observations Regarding Combined Perineural Midazolam-Clonidine-Buprenorphine-Dexamethasone

In a separate commentary [1], we reported on potential clinical research priorities with respect to multimodal perineural anesthesia and analgesia (MMPNA). This was based on our groups review of institutional quality assurance/improvement (QA/QI) data routinely using this technique for over 1,300 patients from late 2011 to the present at the Veterans Affairs Pittsburgh Healthcare System. This previous commentary addressed the four-drug combination of bupivacaine, clonidine, buprenorphine, and dexamethasone (BPV-CBD) used for postoperative perineural analgesia (e.g., combined with intraoperative spinal anesthesia), or for the dual role of intraoperative perineural anesthesia and postoperative analgesia. The average block duration (block insertion time until peak rebound pain score on a 0 to 10 scale) in this previous commentary was 33 to 37 hours, depending on the context. We believe that this clinical observation warrants high-priority research for the specialty, especially in the context of the effects of buprenorphine dose response and the parameters of block duration and rebound pain. In this current commentary, we will direct separate attention toward the four-drug combination of midazolam (MDZ) with CBD used for specific contexts of motor-sparing perineural analgesia. Both BPV-CBD and MDZ-CBD four-drug nerve block combinations were shown to be safe in vivo, as reported in a separate manuscript [2] in this issue of Pain Medicine . Based on the previously reported in vitro safety of MDZ-CBD [3], we used MDZ-CBD blocks in selected cases where the risk of motor block (and subsequent falls) was deemed as high as the potential short- and long-term risks of escalating systemic opioid analgesia (and/or intraoperative conversion to general endotracheal anesthesia [GETA]). All patients were fully informed before the use of MDZ-CBD as an “off-label” good-faith effort to 1) avoid motor block (i.e., routinely resulting from perineural bupivacaine use with or without perineural CBD use); 2) avoid GETA; and …

Improving Pain Management Communication: How Patients Understand the Terms “Opioid” and “Narcotic”

Background/ObjectivesPain specialists often advocate discontinuing use of the term “narcotic,” with the negative connotations it bears for many patients, in favor of the term “opioid.” To contribute empirical data to this argument, we elicited and compared patient understandings of the terms “narcotic” and “opioid.”Design/ParticipantsBrief, anonymous surveys were administered to 100 outpatients. Respondents were asked to describe what a narcotic/opioid is, give example(s), explain why someone would take a narcotic/opioid and describe long term consequences of use.ResultsOf the 100 outpatients, 86% responded “don’t know” to all four opioid questions. Only 12% did not know what a narcotic was (p < 001). While 50% of patients related “narcotics” to pain management, more than a third cited addiction or abuse. Of the 100 outpatients, 78% feared an adverse outcome from long-term narcotic use, with 66% of those answers citing “addiction.”ConclusionMost patients were unfamiliar with the term opioid, while a substantial percentage identified a narcotic as an illegal drug and most reported adverse consequences as the outcome of long term use. Our findings, while preliminary, suggest that “opioid” is a more unfamiliar term, but raise questions about whether simply using different terminology would affect patient fears about this class of medications.

GlideScope Use improves intubation success rates: an observational study using propensity score matching.

BackgroundRigid video laryngoscopes are popular alternatives to direct laryngoscopy for intubation, but further large scale prospective studies comparing these devices to direct laryngoscopy in routine anesthesiology practice are needed. We hypothesized that the first pass success rate with one particular video laryngoscope, the GlideScope, would be higher than the success rate with direct laryngoscopy.Methods3831 total intubation attempts were tracked in an observational study comparing first-pass success rate using a Macintosh or Miller-style laryngoscope with the GlideScope. Propensity scoring was then used to select 626 subjects matched between the two groups based on their morphologic traits.ResultsComparing the GlideScope and direct laryngoscopy groups suggested that intubation would be more difficult in the GlideScope group based on the Mallampati class, cervical range of motion, mouth opening, dentition, weight, and past intubation history. Thus, a propensity score based on these factors was used to balance the groups into two 313 patient cohorts. Direct laryngoscopy was successful in 80.8% on the first-pass intubation attempt, while the GlideScope was successful in 93.6% (p <0.001; risk difference of 0.128 with a 95% CI of 0.0771 – 0.181).ConclusionA greater first-attempt success rate was found when using the GlideScope versus direct laryngoscopy. In addition, the GlideScope was found to be 99% successful for intubation after initial failure of direct laryngoscopy, helping to reduce the incidence of failed intubation.