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Background: The perioperative inflammatory response as measured by elevated levels of interleukin-6 (IL-6) has been linked to acute respiratory distress syndrome, postoperative confusion, and fever. Because of the extent of surgery,patients undergoing bilateral total knee arthroplasty may be at high risk of complications. We had found a significant decrease in IL-6 in patients having bilateral total knee replacement who received two doses of 100 mg of hydrocortisone eight hours apart; however, by twenty-four hours, IL-6 levels were equal to those in the group that received a placebo. In the present study, we investigated whether the administration of three doses would reduce IL-6 levels at twenty-four hours and affect other outcomes such as desmosine level, a marker of lung injury.Methods: After institutional review board approval, a total of thirty-four patients (seventeen patients and seventeen control subjects) were enrolled in this double-blind, randomized, placebo-controlled study. Three doses of intravenous hydrocortisone (100 mg) or placebo were given eight hours apart. Urinary desmosine levels were obtained at baseline and at one and three days postoperatively. The level of IL-6 was measured at baseline and at six, ten, twenty-four, and forty-eight hours postoperatively. Pain scores, presence of fever, and functional outcomes were recorded.Results: The level of IL-6 increased in both groups, but was significantly higher in the control group, peaking at twenty-four hours (mean and standard deviation, 623.74 ± 610.35 pg/mL versus 148.13 ± 119.35 pg/mL; p = 0.006). Urinary desmosine levels significantly increased by twenty-four hours in the control group, but remained unchanged in the study group (134.75 ± 67.88 pmol/mg and 79.45 ± 46.30 pmol/mg, respectively; p = 0.006). Pain scores at twenty-four hours were significantly lower in the study group (1.4 ± 0.9 versus 2.4 ± 1.2; p = 0.01) as was the presence of fever (11.8%versus 47.1%; p = 0.03). Range of motion at the knee was significantly greater in the study group (81.6 ± 11.6 versus 70.6 ± 14.0 in the right knee [p = 0.02] and 81.4 ± 11.3 versus 73.4 ± 9.4 in the left knee [p = 0.03]).Conclusions: Hydrocortisone (100 mg) given over three doses, each eight hours apart, decreased and maintained a lower degree of inflammation with bilateral total knee replacement as measured by IL-6 level. Corticosteroids decreased the prevalence of fever, lowered visual analog pain scores, and improved knee motion. The significantly lower values of desmosine in the study group suggest that this treatment may be protective against lung injury. [ABSTRACT FROM AUTHOR]

Background: Postoperative delirium (POD) is one of the most common complications in older adult patients undergoing elective surgery. Few studies have compared, within the same institution, the type of surgery, risk factors and type of anesthesia and analgesia associated with the development of POD., Aim: To investigate the following three questions: (1) What is the incidence of POD after non-ambulatory orthopedic surgery at a high-volume orthopedic specialty hospital? (2) Does surgical procedure influence incidence of POD after non-ambulatory orthopedic surgery? And (3) For POD after non-ambulatory orthopedic surgery, what are modifiable risk factors?, Methods: A retrospective cohort study was conducted of all non-ambulatory orthopedic surgeries at a single orthopedic specialty hospital between 2009 and 2014. Patients under 18 years were excluded from the cohort. Patient characteristics and medical history were obtained from electronic medical records. Patients with POD were identified using International Classification of Diseases, 9 th Revision (ICD-9) codes that were not present on admission. For incidence analyses, the cohort was grouped into total hip arthroplasty (THA), bilateral THA, total knee arthroplasty (TKA), bilateral TKA, spine fusion, other spine procedures, femur/pelvic fracture, and other procedures using ICD-9 codes. For descriptive and regression analyses, the cohort was grouped, using ICD-9 codes, into THA, TKA, spinal fusions, and all procedures., Results: Of 78492 surgical inpatient surgeries, the incidence from 2009 to 2014 was 1.2% with 959 diagnosed with POD. The incidence of POD was higher in patients undergoing spinal fusions (3.3%) than for patients undergoing THA (0.8%); THA patients had the lowest incidence. Also, urgent and/or emergent procedures, defined by femoral and pelvic fractures, had the highest incidence of POD (7.2%) than all other procedures. General anesthesia was not seen as a significant risk factor for POD for any procedure type; however, IV patient-controlled analgesia was a significant risk factor for patients undergoing THA [Odds ratio (OR) = 1.98, 95% confidence interval (CI): 1.19 to 3.28, P = 0.008]. Significant risk factors for POD included advanced age (for THA, OR = 4.9, 95%CI: 3.0-7.9, P < 0.001; for TKA, OR = 2.16, 95%CI: 1.58-2.94, P < 0.001), American Society of Anesthesiologists score of 3 or higher (for THA, OR = 2.01, 95%CI: 1.33-3.05, P < 0.001), multiple medical comorbidities, hyponatremia (for THA, OR = 2.36, 95%CI: 1.54 to 3.64, P < 0.001), parenteral diazepam (for THA, OR = 5.05, 95%CI: 1.5-16.97, P = 0.009; for TKA, OR = 4.40, 95%CI: 1.52-12.75, P = 0.007; for spine fusion, OR = 2.17, 95%CI: 1.19-3.97, P = 0.01), chronic opioid dependence (for THA, OR = 7.11, 95%CI: 3.26-15.51, P < 0.001; for TKA, OR = 2.98, 95%CI: 1.38-6.41, P = 0.005) and alcohol dependence (for THA, OR = 5.05, 95%CI: 2.72-9.37, P < 0.001; for TKA, OR = 6.40, 95%CI: 4.00-10.26, P < 0.001; for spine fusion, OR = 6.64, 95%CI: 3.72-11.85, P < 0.001)., Conclusion: POD is lower (1.2%) than previously reported; likely due to the use of multi-modal regional anesthesia and early ambulation. Both fixed and modifiable factors are identified., Competing Interests: Conflict-of-interest statement: Each author certifies that Sasaki M has received research support funding from Susan and Elihu Rose Foundation. Each author certifies that Schmucker AM has received research support funding from Susan and Elihu Rose Foundation., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: The treatment of postoperative pain is a challenge after posterior spinal fusions. Pain management using predominantly opioids is often associated with multiple adverse effects, while multimodal postoperative analgesia may provide adequate pain relief with fewer opioid side effects., Questions/purposes: The purpose of this review is to determine whether addition of 150 mg pregabalin daily would reduce narcotic requirements and improve outcomes after posterior lumbar fusion (PLF)., Methods: The method used is a randomized, controlled trial of elective PLF patients who received pregabalin or placebo. With institutional review board (IRB) approval, 86 patients undergoing elective posterior lumbar fusion, ASA I-III, were randomized to receive either a placebo or pregabalin after obtaining written informed consent. Both arms, i.e., placebo and pregabalin, consisted of 43 patients each.The 86 patients for elective PLF were randomly assigned to receive 150 mg of pregabalin 1 h before surgery and then 150 mg daily, or a placebo tablet. All patients received a similar general anesthetic and in the post-anesthesia care unit (PACU), started on intravenous (IV) patient-controlled analgesia (PCA) of hydromorphone (0.2 mg/ml). Postoperative pain was assessed daily until discharge using a Numerical Rating Scale (NRS) at rest and with physical therapy (PT). Patients were also assessed twice daily for level of sedation and nausea and/or vomiting and expected PT milestones. All narcotics (IV, oral) were documented., Results: Demographics and operative time between groups were similar. PCA hydromorphone administration and oral narcotic intake were not statistically different between the two groups. However, an increased incidence of nausea and vomiting in the placebo group reached statistical significance ( p  < 0.05). In addition, there was no statistical difference between groups with respect to achieving PT milestones and hospital discharge day., Conclusion: After PLF, patients receiving pregabalin 150 mg/day did not have reduced IV narcotic usage, improved PT milestones, or reduced length of hospital stay. We were unable to demonstrate an analgesic advantage to prescribing pregabalin to patients undergoing lumbar spinal fusions., Competing Interests: Compliance with Ethical StandardsMichael K. Urban, MD, PhD; Kristy M. Labib, MD; Shane C. Reid, MBS, BA; Amanda K. Goon, BA; and Valeria Rotundo have declared that they have no conflict of interest. Frank P. Cammisa Jr MD reports royalties for patent with NuVasive. Federico P. Girardi, MD reports royalties paid for patents with DePuy Spine, LANX, Inc., NuVasive, and Ortho Development Corp., outside the work.All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008 (5).Informed consent was obtained from all patients for being included in the study.Disclosure forms provided by the authors are available with the online version of this article.

Background Context: Lidocaine has emerged as a useful adjuvant anesthetic agent for cases requiring intraoperative monitoring of motor-evoked potentials (MEPs) and somatosensory-evoked potentials (SSEPs). A previous retrospective study suggested that lidocaine could be used as a component of propofol-based intravenous anesthesia without adversely affecting MEP or SSEP monitoring, but did not address the effect of the addition of lidocaine on the MEP and SSEP signals of individual patients., Purpose: The purpose of this study was to examine the intrapatient effects of the addition of lidocaine to balanced anesthesia on MEPs and SSEPs during multilevel posterior spinal fusion., Study Design: This is a prospective, two-treatment, two-period crossover randomized controlled trial with a blinded primary outcome assessment., Patient Sample: Forty patients undergoing multilevel posterior spinal fusion were studied., Outcome Measures: The primary outcome measures were MEP voltage thresholds and SSEP amplitudes. Secondary outcome measures included isoflurane concentrations and hemodynamic parameters., Methods: Each participant received two anesthetic treatments (propofol 50 mcg/kg/h and propofol 25 mcg/kg/h+lidocaine 1 mg/kg/h) along with isoflurane, ketamine, and diazepam. In this manner, each patient served as his or her own control. The order of administration of the two treatments was determined randomly., Results: There were no significant within-patient differences between MEP threshold voltages or SSEP amplitudes during the two anesthetic treatments., Conclusions: Lidocaine may be used as a component of balanced anesthesia during multilevel spinal fusions without adversely affecting the monitoring of SSEPs or MEPs in individual patients., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Orthopedic patients with ischemic heart disease are at risk for postoperative cardiac complications., Questions/purposes: Using information from two medical information retrieval systems which insured the capture of all events for the period of study, our goals were to determine the incidence of myocardial injury in at-risk patients after orthopedic surgery and to delineate the type and incidence of cardiac complications in this population., Methods: For one year, at an orthopedic hospital, we identified all postoperative patients with a measured cTnI level using an electronic ordering system. Preoperative cardiac risk factors and postoperative cardiac complications were identified in patients undergoing a total hip arthroplasty (THA), total knee arthroplasty (TKA), and posterior spinal fusion (PSF). A postoperative myocardial infarction was defined by a cTnI > 0.1 ng/mL, ECG changes, new echocardiographic regional wall motion abnormalities, and evaluation by a cardiologist. Categorical variables were compared among groups with a Fisher's exact or Chi-square test. Continuous variables were compared among groups with ANOVA or the Kruskal-Wallis test. The associations of cardiac risk factors with myocardial injury are expressed as odds ratios from logistic regression models., Results: During a one-year period, from 10,627 inpatient orthopedic procedures, 805 patients were identified as at risk for postoperative myocardial ischemia. A total of 20.6% (166/805) of these patients had elevated serum cTnI levels (cTnI > 0.02 ng/mL), and there were ten documented postoperative MIs (10/805; 1.2%). For the at-risk TKA, THA, or PSF patients, 19% (102/532) had elevated cTnI levels and 31% (32/102) had postoperative cardiac complications, including arrhythmias (56%), congestive heart failure (2%), and MI (1%). Adjusting for sex, age, BMI, cardiac risk factors, and medications (statins and β-blockers), PSF patients had 3.9 times the risk of myocardial injury ( p  = 0.003) compared to TKA patients and 4.2 times that of THA patients., Conclusions: The incidence of postoperative myocardial ischemia after major orthopedic surgery in patients with cardiac risk factors is high (8.7%), but the incidence of documented myocardial infarctions and serious cardiac complications remains low (1.2-2%). Patients with higher postoperative cTnI releases were more likely to have cardiac complications, and some procedures (spinal fusions) placed the patients at a higher risk.

Background: The goal of elective orthopedic surgery is to return patients to their expected level of activity without an increased incidence of postoperative complications. The first step is identifying patient and/or surgical characteristics responsible for these complications., Questions/purposes: This study sought to identify predictors of a step-up in medical care after non-ambulatory elective orthopedic surgery., Methods: At a single specialty orthopedic hospital, we identified all in-hospital postoperative patients who were transferred to a higher level of medical care ((PACU) post-anesthesia care unit). The characteristics of both transferred and non-transferred patients were compared. A model was built which incorporated predictors of return to a higher level of care., Results: During a 1-year period, 155 of 7967 patients (1.95%) required transfer to the PACU within 5 days of surgery. Cardiac complications were the major reason for transfer (50.3%), followed by pulmonary (11.0%) and neurological complications (9.7%). Patients who returned to the PACU were older, had more Exlihauser comorbidities, and had obstructive sleep apnea (OSA). In a model adjusting for all patient characteristics: age, American Society of Anesthesiologists (ASA) status, congestive heart failure (CHF), the Charlson comorbidity index and OSA predicted return to the PACU., Conclusions: In an elderly population with multiple comorbidities undergoing elective common major orthopedic procedures, approximately 2% of patients required readmission to the PACU. The most common problems requiring this step-up in care were cardiac and pulmonary, which resulted in an increased length of hospital stay. Patients with OSA and multiple comorbidities undergoing total knee arthroplasty carry an increased risk for postoperative complications.

Objectives: The authors investigated the impact of computerized provider order entry (CPOE) on the delivery times of analgesia and subsequent patient outcomes. We hypothesized that patients would report less pain and use less pain medications compared with the previous paper-based system., Methods: Two groups of patients after a total hip (THA) or knee arthroplasty (TKA) were retrospectively compared: one comprising 106 patients when the paper-based ordering system was in effect (conventional group), and one comprising 96 patients after CPOE was installed (electronic group). All patients received a regional anaesthetic at surgery (combined spinal-epidural). TKA patients also received a single-injection femoral nerve block. After transfer to the postoperative anaesthesia care unit (PACU), a patient-controlled epidural analgesia (PCEA) infusion was initiated. The following data was collected from the PACU record: time to initiation of analgesia, visual analog scale (VAS) pain scores at initiation of analgesia and hourly for the first postoperative day (POD), volume of pain medication used, length of stay (LOS) in the PACU and the hospital., Results: The time to initiation of analgesia from arrival in the PACU was significantly lower in the electronic group compared to the conventional group (24.5 ± 28.3 minutes vs. 51.1 ± 26.2 minutes; mean ± SD, p < 0.001), as were VAS pain scores (0.82 ± 1.08 vs. 1.5 ± 1.52, p < 0.001) and the volume of PCEA needed to control pain (27.9 ± 20.2 ml vs. 34.8 ± 20.3 ml, p = 0.001) at 4 hours postoperatively. PACU LOS and hospital LOS did not significantly differ in the two groups., Conclusions: After implementation of CPOE, patients received their postoperative analgesia faster, had less pain, and required less medication.

Background: A substantial fraction of all American healthcare expenditures are potentially wasted, and practices that are not evidence-based could contribute to such waste. We sought to characterize whether Prothrombin Time (PT) and activated Partial Thromboplastin Time (aPTT) tests of preoperative patients are used in a way unsupported by evidence and potentially wasteful., Methods and Findings: We evaluated prospectively-collected patient data from 19 major teaching hospitals and 8 hospital-affiliated surgical centers in 7 states (Delaware, Florida, Maryland, Massachusetts, New Jersey, New York, Pennsylvania) and the District of Columbia. A total of 1,053,472 consecutive patients represented every patient admitted for elective surgery from 2009 to 2012 at all 27 settings. A subset of 682,049 patients (64.7%) had one or both tests done and history and physical (H&P) records available for analysis. Unnecessary tests for bleeding risk were defined as: PT tests done on patients with no history of abnormal bleeding, warfarin therapy, vitamin K-dependent clotting factor deficiency, or liver disease; or aPTT tests done on patients with no history of heparin treatment, hemophilia, lupus anticoagulant antibodies, or von Willebrand disease. We assessed the proportion of patients who received PT or aPTT tests who lacked evidence-based reasons for testing., Conclusions: This study sought to bring the availability of big data together with applied comparative effectiveness research. Among preoperative patients, 26.2% received PT tests, and 94.3% of tests were unnecessary, given the absence of findings on H&P. Similarly, 23.3% of preoperative patients received aPTT tests, of which 99.9% were unnecessary. Among patients with no H&P findings suggestive of bleeding risk, 6.6% of PT tests and 7.1% of aPTT tests were either a false positive or a true positive (i.e. indicative of a previously-undiagnosed potential bleeding risk). Both PT and aPTT, designed as diagnostic tests, are apparently used as screening tests. Use of unnecessary screening tests raises concerns for the costs of such testing and the consequences of false positive results.

Background: Traditionally, blood transfusions in the perioperative setting are used to maintain adequate delivery of nutrients and oxygen to organs. However, the effect of blood administration on tissue oxygenation in the perioperative setting remains poorly understood., Questions/purposes: The aim of this study was to determine changes in muscle tissue oxygenation saturation (SmO2) in response to perioperative blood transfusions., Patients and Methods: Patients undergoing total knee arthroplasty were enrolled. SmO2, continuous hemoglobin (SpHb), stroke volume (SV), cardiac index, and standard hemodynamic parameters including heart rate (HR), mean arterial blood pressure (MAP), and arterial oxygen saturation (SO2) were recorded. To assess fluid responsiveness, a passive leg raise (PLR) test was performed before the transfusions were started., Results: Twenty-eight patients were included in the analysis. Mean (±SD) SmO2 before transfusion was 63.18 ± 10.04%, SpHb was 9.27 ± 1.16 g/dl, and cardiac index was 2.62 ± 0.75 L/min/m(2). A significant increase during the course of blood transfusion was found for SmO2 (+3.44 ± 5.81% [95% confidence interval (CI) 1.04 to 5.84], p = 0.007), SpHb (0.74 ± 0.92 g/dl [95% CI 0.35 to 1.12], p < 0.001), and cardiac index (0.38 ± 0.51 L/min/m2 [95% CI 0.15 to 0.60], p = 0.002), respectively. However, the correlation between SmO2 and SpHb over the course of the transfusion was negligible (ρ = 0.25 [95% CI -0.03 to 0.48]). A similar lack of correlation was found when analyzing data of those patients who showed a positive leg raise test before the start of the transfusion (ρ = 0.37 [95% CI -0.11 to 0.84])., Conclusion: We detected a statistically significant increase in SmO2 during the course of a single unit blood transfusion compared to baseline. However, there was no evidence of a correlation between longitudinal SmO2 and SpHb measurements.

Background: Pulmonary hypertension (PH) is regarded as a risk factor for perioperative complications in patients undergoing noncardiac surgery., Questions/purposes: The objective of this retrospective case-control study was to evaluate the adverse outcomes of pulmonary hypertension patients undergoing elective unilateral hip replacements., Methods: We performed a retrospective case-control study of total hip replacement patients with pulmonary hypertension (cases) and without pulmonary hypertension (control). From the years 2003 to 2008, we identified a total of 132 patients undergoing primary total hip replacements with a diagnosis of pulmonary hypertension (right ventricular systolic pressure >35). The primary outcome assessed was the incidence of adverse events that occurred during the postoperative hospital stay. Secondary outcomes studied included length of hospital stay, mortality, and ability to reach certain physical therapy milestones., Results: The PH group had significantly more adverse events than the control group. Nonlethal cardiac dysrhythmias comprised the most common adverse outcome among the PH group. Overall, the PH group had a morbidity rate of 34.7% while the control had a rate of 21%. The PH group had longer hospital stay (6.7 days vs. 5.9). Both groups had zero mortality during the hospital stay. The PH group had comparable rehabilitation recovery times than the control group., Conclusion: This retrospective case-control study demonstrates that pulmonary hypertension patients undergoing total hip arthroplasty are more prone to adverse outcomes, especially cardiac dysrhythmias, and longer hospital stays.

Mutations in LRRK2, encoding the multifunctional protein leucine-rich repeat kinase 2 (LRRK2), are a common cause of Parkinson disease. LRRK2 has been suggested to influence the cytoskeleton as LRRK2 mutants reduce neurite outgrowth and cause an accumulation of hyperphosphorylated Tau. This might cause alterations in the dynamic instability of microtubules suggested to contribute to the pathogenesis of Parkinson disease. Here, we describe a direct interaction between LRRK2 and β-tubulin. This interaction is conferred by the LRRK2 Roc domain and is disrupted by the familial R1441G mutation and artificial Roc domain mutations that mimic autophosphorylation. LRRK2 selectively interacts with three β-tubulin isoforms: TUBB, TUBB4, and TUBB6, one of which (TUBB4) is mutated in the movement disorder dystonia type 4 (DYT4). Binding specificity is determined by lysine 362 and alanine 364 of β-tubulin. Molecular modeling was used to map the interaction surface to the luminal face of microtubule protofibrils in close proximity to the lysine 40 acetylation site in α-tubulin. This location is predicted to be poorly accessible within mature stabilized microtubules, but exposed in dynamic microtubule populations. Consistent with this finding, endogenous LRRK2 displays a preferential localization to dynamic microtubules within growth cones, rather than adjacent axonal microtubule bundles. This interaction is functionally relevant to microtubule dynamics, as mouse embryonic fibroblasts derived from LRRK2 knock-out mice display increased microtubule acetylation. Taken together, our data shed light on the nature of the LRRK2-tubulin interaction, and indicate that alterations in microtubule stability caused by changes in LRRK2 might contribute to the pathogenesis of Parkinson disease.

Background: Interleukin 6 (IL-6), a marker of inflammation, is one of the major cytokines released during joint replacement. In the orthopedic patient population, high levels have been linked to many adverse effects including acute respiratory distress syndrome, postoperative mental status changes, and fever. We looked to assess the efficacy of low-dose steroids on the postinflammatory response as measured by IL-6 in patients undergoing bilateral total knee replacement (BTKR). The role of steroids has never been evaluated before in that setting., Methods: Double-blind, randomized, placebo-controlled study of 30 patients undergoing BTKR. The study was powered in order to detect at least a 25% decrease in IL-6 from control. Hydrocortisone (100 mg) or placebo was given at 2 doses 8 hrs apart to the study and control group respectively. Clinical outcome was assessed as well., Results: Levels of IL-6 were 40% lower in the study group by 10 hrs (P = 0.0037) but were similar to the control group at 24 hrs. Greater hemodynamic stability was noted in the study group with fewer episodes of hypotension postoperatively (P = 0.031). Range of motion gained on discharge was also greatest in the study group (P = 0.049). Absence of infection and normal wound healing were noted in all patients., Conclusions: The use of hydrocortisone significantly decreased the inflammatory response in patients undergoing BTKR as measured by IL-6 production. Further studies looking at clinical implications of such findings in a larger patient population and with a longer course of steroids are warranted.

The objective of this prospective observational study was to determine if urine desmosine levels, a marker of lung injury, increase in response to the periopreative insults of anterior and posterior spine surgery. Desmosine, a stable breakdown product of elastin, has been proposed as a surrogate marker of lung injury in patients with COPD, tobacco use, and ARDS. We recently evaluated this marker in patients undergoing knee surgery, but the utility of desmosine as a marker of lung injury in patients undergoing spine surgery remains unstudied. In this study, we enrolled ten consecutive patients, who underwent anterior/posterior spine surgery. Patient demographics and perioperative data were recorded. Urine samples were collected at baseline, 1 day, and 3 days postoperatively and analyzed for levels of desmosine using a previously validated radioimmunoassay. Desmosine levels were 35.9 ± 18.2 pmol/mg creatinine at baseline, 38.7 ± 11 pmol/mg creatinine on postoperative day 1, and 70.5 ± 49.1 pmol/mg creatinine on postoperative day 3, respectively. Desmosine/creatinine ratios measured on day 3 postoperatively were significantly elevated compared to levels at baseline, and represented a 96.3% increase. No difference was seen between levels at baseline and day 1 postoperatively. In conclusion, we were able to show a significant increase in urine desmosine levels associated with anterior/posterior spine surgery. In the context of previous studies, our findings suggest that desmosine may be a marker of lung injury in this setting. However, further research is warranted for validation and correlation of desmosine levels to clinical markers and various degrees of lung injury.

Background and Objectives: The transarterial axillary block and the ultrasound-guided infraclavicular block are both effective methods of anesthetizing the upper extremity. This study compares these methods with respect to subjective postoperative dysesthesias, block adequacy, patient comfort, and patient satisfaction., Methods: Two hundred thirty-two patients were randomized to receive an ultrasound-guided infraclavicular block or a transarterial axillary block for upper extremity surgery. Block placement, motor and sensory testing, and block adequacy data were recorded. The subjects were contacted by a blinded research assistant at 2 and 10 days postoperatively to assess for the presence of dysesthesias and pain and to assess patient satisfaction., Results: The 2 techniques were similar with respect to block performance time and adequacy of the block for surgery. There was no significant difference between the blocks in terms of postoperative dysesthesias (23.9% in the axillary group vs 17.1% in the infraclavicular group at 2 days, P = 0.216, and 11.0% vs 6.31% at 10 days, P = 0.214). None of the dysesthesias were permanent. The infraclavicular block had a lower incidence of paresthesias during placement (P = 0.035) and was associated with less pain at the block site (P = 0.010 at 2 days, P = 0.002 at 10 days). More patients were willing to undergo the infraclavicular block as a future anesthetic when compared with the axillary block (P = 0.025 at 10 days)., Conclusions: There is no significant difference between the 2 techniques in terms of adequacy for surgery and subjective postoperative dysesthesias. The ultrasound-guided infraclavicular block is associated with greater patient comfort and willingness to undergo the same anesthetic when compared with the transarterial axillary block.

Bilateral total knee replacement (BTKR) has been associated with a higher incidence of fat embolism (FES) compared to single knee replacement. Consequently, intraoperative monitoring with a pulmonary artery catheter (PAC) has been recommended. This study compares clinical outcome in BTKR patients monitored with central venous pressure versus PAC. A retrospective chart review of 249 consecutive patients undergoing BTKR, 132 of whom had PAC insertion versus 117 who had central line insertion, over a 1-year period were included in the study. Their medical records were reviewed for co-morbidities, baseline characteristics, and type of intraoperative monitoring. Need and duration for postoperative monitoring in the postoperative care, length of hospital stay (LOHS), signs of fat embolism, development of arrhythmias, and respiratory failure were all outcome measures. A total of four patients (1.6%) had FES as per Schonfeld criteria. One of these patients died within 48 h of surgery. They all had PAC monitoring intraoperatively. Pulmonary artery pressure (PAP) remained unchanged during surgery which raises doubt as to the clinical utility and advisability of the use of PAC's in this setting. There was no statistically significant difference in cardiac or pulmonary complications, or LOHS between the two groups. Central venous pressure monitoring appears to be sufficient in patients undergoing BTKR.

Management of acute postoperative pain is challenging, particularly in patients with preexisting narcotic dependency. Ketamine has been used at subanesthetic doses as a N-methyl D-aspartate (NMDA) receptor antagonist to block the processing of nociceptive input in chronic pain syndromes. This prospective randomized study was designed to assess the use of ketamine as an adjunct to acute pain management in narcotic tolerant patients after spinal fusions. Twenty-six patients for 1-2 level posterior lumbar fusions with segmental instrumentation were randomly assigned to receive ketamine or act as a control. Patients in the ketamine group received 0.2 mg/kg on induction of general anesthesia and then 2 mcg kg(-1) hour(-1) for the next 24 hours. Patients were extubated in the operating room and within 15 minutes of arriving in the Post Anesthesia Care Unit (PACU) were started on intravenous patient-controlled analgesia (PCA) hydromorphone without a basal infusion. Patients were assessed for pain (numerical rating scale [NRS]), narcotic use, level of sedation, delirium, and physical therapy milestones until discharge. The ketamine group had significantly less pain during their first postoperative hour in the PACU (NRS 4.8 vs 8.7) and continued to have less pain during the first postoperative day at rest (3.6 vs 5.5) and with physical therapy (5.6 vs 8.0). Three patients in the control group failed PCA pain management and were converted to intravenous ketamine infusions when their pain scores improved. Patients in the ketamine group required less hydromorphone than the control group, but the differences were not significant. Subanesthetic doses of ketamine reduced postoperative pain in narcotic tolerant patients undergoing posterior spine fusions.

The diagnosis of a postoperative myocardial infarction (PMI) is important in the orthopedic population because these events can be associated with significant cardiac morbidity. Plasma troponin I (cTnI) analysis has markedly increased our ability to detect myocardial damage. Using cTnI analysis for evidence of a PMI, we prospectively assessed all of our patients for (1) the 1-year incidence of PMI, (2) the clinical consequences of a PMI in relation to the level of the cTnI release, and (3) 6-month follow-up for cardiac complications. During a 12-month period, patients at risk for perioperative myocardial ischemia were assessed for a PMI by serum cTnI levels and daily serial ECGs. Patients with cTnI levels above the reference level (> or = 0.4 ng/ml) were also assessed for new cardiac regional wall motion abnormalities with an echocardiogram and 6-month postdischarge adverse cardiac events. Of the 758 patients who were assessed for a PMI, 49 patients had detectable cTnI levels (> or = 0.4 ng/ml); the incidence of a PMI was 0.6% of all surgical cases and 6.5% of those patients were at risk for a cardiac event. A PMI was more common after hip arthroplasty than other orthopedic procedures. Twenty-three patients had a cTnI level >3.0 ng/ml, and 74% these patients (17/23) had anginal symptoms and/or ischemic ECG changes. Nine of these patients (9/23) had new postoperative echocardiographic changes, five (5/23) required emergency transfer to a cardiac care unit, and 10 (10/23) had postoperative cardiac complications. In contrast, 15 patients with levels of cTnI <3.0 ng/ml and without ischemic ECG changes and/or anginal symptoms had no postoperative cardiac complications. Fourteen patients (14/47) had cardiac complications 6 months after discharge, including four cardiac deaths, one fatal stroke, and four patients with unstable anginal episodes that required a change in medical management, and six patients required coronary revascularization. Orthopedic surgical patients with cTnI level <3 ng/ml and without symptoms or ECG changes suggestive of myocardial ischemia (15/49) may have different risks than those with higher-level cTn1.

Interscalene block (ISB) of the brachial plexus is frequently used for patients undergoing ambulatory shoulder surgery. We previously reported that the incidence of postoperative complaints (neurapraxia) after an ISB was low (3% at 2 weeks), but objective neurologic assessment was not included in the study. The present study combines subjective findings with both preoperative and postoperative objective sensory and motor assessments after an ISB. We prospectively evaluated 133 patients undergoing elective ambulatory shoulder surgery. ISB anesthesia was accomplished by use of 1.5% mepivacaine alone or in combination with bupivacaine (0.5%-0.75%) via a paresthesia technique and a 23-gauge needle. All of the blocks were performed by experienced anesthesiologists. The number of passes with the needle, site of paresthesia, ease of performing the block, and success of the ISB were recorded for each patient. Neurologic assessment was performed preoperatively and up to 2 weeks postoperatively by 1 of 4 health care professionals but not by the anesthesiologists who performed the ISB and included diminished sensation, localized nerve pain, Semmes-Weinstein monofilament pressure threshold sensibility, Weber static 2-point discrimination, and grip strength changes. Patients with postoperative changes were followed up until resolution of symptoms occurred. Successful surgical anesthesia was achieved in 98% of the patients. There was 1 major perioperative complication (0.7%), a seizure that occurred within 5 minutes of the ISB. Two (1.4%) complained of transient postoperative neurapraxias. Neither patient had any changes in objective sensory and motor measurements. Hence, there was no correlation between subjective complaints and objective findings in this study. This study demonstrates that, in the hands of anesthesiologists doing predominantly regional anesthesia, there is a 1.4% incidence of neurologic complications after an ISB. ISB is a safe and effective technique for patients undergoing ambulatory shoulder surgery when an anesthesiologist experienced with regional anesthesia is involved.

Background Context: Lumbar microdiscectomy is most commonly performed under general anesthesia, which can be associated with several perioperative morbidities including nausea, vomiting, atelectasis, pulmonary aspiration, and prolonged post-anesthesia recovery. It is possible that fewer complications may occur if the procedure is performed under epidural anesthesia., Purpose: To investigate the safety and efficacy of epidural anesthesia in elective lumbar microdiscectomies., Study Design: A prospective study evaluating the relative morbidities associated with epidural anesthesia and general anesthesia for lumbar microdiscectomy., Patient Sample: Forty-three patients scheduled for primary lumbar microdiscectomy. Two cohorts were formed and were studied separately; one observational of all the 43 patients, and a second cohort of 17 patients who agreed to enter in the randomized trial., Outcome Measures: The clinical outcome was determined by the presence of postoperative pain, the absence of anesthesia-related complications, and the overall postoperative recovery., Methods: This was a prospective study. With institutional review board approval, 43 consecutive patients were enrolled in the study. However, only 17 patients agreed to be randomized to receive either general or epidural anesthesia for the procedure; the remaining 26 patients selected the type of anesthesia of their preference. Recorded data for all patients included: age; total surgical time; occurrence of nausea, vomiting, atelectasis, or cardiopulmonary complication; ability to arise out of bed on the day of surgery; and the total number of inpatient hospital days. Postoperative pain and satisfaction were assessed only in the randomized cohort., Results: There were a total of 43 patients, with a mean age of 38.1 years. The patients undergoing epidural anesthesia were marginally older than those undergoing general anesthesia. The epidural and general anesthetic groups were not different with respect to surgical time, pain assessed with a linear visual analogue scale, hospital stay, or the likelihood of arising out of bed on the day of surgery. There were no major cardiopulmonary complications in either group. Patients with epidural anesthesia had significantly less nausea and vomiting., Conclusions: Epidural anesthesia as an alternative to general anesthesia has shown less postoperative nausea and vomiting in lumbar microdiscectomy. Nevertheless, given the small number of patients, this study should be considered as preliminary, showing small differences in minor potential complications.

Study Design: Case report., Objectives: To report on a patient with Pott disease, progressive neurologic deficit, and severe kyphotic deformity, who had medical treatment fail and required posterior/anterior decompression with instrumented fusion. Treatment options will be discussed., Summary of Background Data: Tuberculous spondylitis is an increasingly common disease worldwide, with an estimated prevalence of 800,000 cases., Methods: Surgical treatment consisting of extensive posterior decompression/instrumented fusion and 3-level posterior vertebral column resection, followed by anterior debridement/fusion with cage reconstruction., Results: Neurologic improvement at 6-month follow-up (Frankel B to Frankel D), with evidence of radiographic fusion., Conclusions: A 70-year-old patient with progressive Pott paraplegia and severe kyphotic deformity, for whom medical treatment failed is presented. A posterior vertebral column resection, multiple level posterior decompression, and instrumented fusion, followed by an anterior interbody fusion with cage was used to decompress the spinal cord, restore sagittal alignment, and debride the infection. At 6-month follow-up, the patient obtained excellent pain relief, correction of deformity, elimination of the tuberculous foci, and significant recovery of neurologic function.

A significant number of patients with degenerative arthritis of the knee require bilateral knee arthroplasty. Single-stage bilateral total knee arthroplasty (SBTKR) has been associated with increased patient morbidity and mortality. At our institution, the following steps have been taken to minimize the risks to patients undergoing this procedure: regional anesthesia and analgesia, invasive monitoring, postoperative observation in an intensive care unit setting, and aggressive management of hemodynamic aberrations. We reviewed the medical records of 462 sequential total knee arthroplasty patients, consisting of 169 SBTKR and 293 unilateral total knee arthroplasty (UTKR) cases. A total of 122 patients from each group were matched for age, weight, and a history of ischemic heart disease and hypertension. Patients for SBTKR exhibited a significantly higher incidence of fat embolism syndrome and cardiac arrhythmias than UTKR patients. There were no deaths in either group and the incidence of other serious postoperative complications was low and similar between the two groups. Elderly patients (approximately 75 years old) had more postoperative complications. With aggressive clinical management SBTKR can be safely performed in selected patients. Guidelines for the selection of these patients are presented.

Background Context: Previous reports have shown that 15% of patients who undergo sequential anterior, then posterior, surgical corrections for spinal deformities demonstrate evidence of acute lung injury. By analyzing the bronchoalveolar lavage (BAL) fluid from these patients for evidence of acute inflammation, we might gain some insight into the etiology of this acute lung injury., Purpose: To elucidate the etiology of acute lung injury after corrective surgery for adult spinal deformities., Study Design/setting: Fifteen adult patients with scoliosis scheduled for elective sequential anterior then posterior corrective (A/P) spinal deformity surgery., Patient Sample: Consecutive adult patients with scoliosis scheduled for elective corrective surgery with the author (OBA)., Outcome Measures: Patients were assessed for postoperative respiratory complications by oxygen requirements, continued mechanical ventilation, and radiological evidence of diffuse bilateral interstitial or alveolar infiltrates. An acute pulmonary inflammatory response included the presence of inflammatory cells and elevated cytokines in BAL fluid., Methods: BAL were performed after induction of anesthesia but before surgery, at the completion of surgery, and on the morning after surgery with the patient still intubated. BAL fluid was analyzed for inflammatory cells and cytokine interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) levels. Patients were assessed postoperatively for increased pulmonary vascular resistance, radiological evidence of diffuse bilateral alveolar infiltrates, and the requirement for ventilatory support beyond the first postoperative day (POD1)., Results: The cell counts of BAL fluid demonstrated significant increases in neutrophils, lymphocytes, and lipid laden macrophages (LLMAC) with surgery. The concentration of the cytokines IL-6 and TNF-alpha also increased with surgery. The elevations in BAL inflammatory cells and cytokine levels correlated positively with increased pulmonary vascular resistance and the requirement for mechanical ventilation., Conclusions: After A/P spine fusions, patients have evidence of an acute inflammatory pulmonary injury. Several etiologies exist for this finding, including blood and fluid infusions, direct trauma to the lung, a systemic inflammatory response, and the embolization of fat and bone-marrow debris. The presence of LLMAC in the lungs of these patients and the finding that the patient with the requirement for the longest ventilatory support also had the highest BAL LLMAC count, suggest that the embolization of fat and bone debris released from the spine during surgery may be at least partially responsible for the lung injury. Further studies on the mechanism of lung injury during this procedure are warranted.

Background Context: Surgery for adult spinal deformity may require both an anterior and posterior approach in order to stabilize the spine and achieve the desired correction. These procedures can be associated with significant pulmonary complications, including atelectasis, pneumonia and respiratory failure. The etiology of some of the respiratory complications is clear: poor inspiratory effort from incision pain and previous pulmonary disease. However, for many patients the direct cause of these complications is not obvious., Purpose: To delineate the incidence, severity and risks associated with pulmonary complications in the setting of major spine surgery., Study Design/setting: Retrospective chart review study of adult patients undergoing combined anterior-posterior thoracic, lumbar and sacral fusion spine surgery., Patient Sample: A total of 60 charts were reviewed for this study., Outcome Measures: Radiographic abnormalities correlated with clinical findings, postoperative need for ventilation and lengths of hospital stay were used as outcome measures., Methods: Perioperative pulmonary complications were assessed for 60 patients with spinal deformities who underwent combined anterior-posterior thoracic, lumbar and sacral fusion over a 2-year period., Results: One patient was eliminated from analysis because of multiple surgeries during his hospital course. Of the remaining 59 patients, 38 (64%) developed roentgenographic abnormalities. The most common radiographic finding was an effusion found in 66% of these patients, followed by atelectasis in 53%. Twenty-one percent (8 of 38) had infiltrates. Five (5 of 38) or 13% had evidence of partial or complete lobar collapse; in two bronchoscopy was required because of profound hypoxemia. Two patients had pneumonia requiring antibiotic treatment. All but two patients were extubated within 36 hours of surgery. They were kept intubated because of hemodynamic instability. There was no statistically significant difference in the group of patients with and without roentgenographic abnormalities with regard to age, weight, American Society of Anesthesiologists class, smoking history, pulmonary function test results, blood loss, perioperative blood and crystalloid requirement and length of surgery. Patients with radiographic abnormalities were more likely to have had invasion of their thoracic cavity (p=.02) and had a longer mean hospital stay of 13.5 versus 10.2 days (p=.009)., Conclusion: Radiographic abnormalities of the lungs are common after major spine surgery involving both an anterior and posterior approach, especially when the thoracic cavity is invaded. In view of the morbidity and longer hospital stay associated with such findings, close monitoring of pulmonary status with aggressive pulmonary toilet are indicated.

The formation of somites, reiterated structures that will give rise to vertebrae and muscles, is thought to be dependent upon a molecular oscillator that may involve the Notch pathway. hairy/Enhancer of split related [E(spl)]-related (her or hes) genes, potential targets of Notch signaling, have been implicated as an output of the molecular oscillator. We have isolated a zebrafish deficiency, b567, that deletes two linked her genes, her1 and her7. Homozygous b567 mutants have defective somites along the entire embryonic axis. Injection of a combination of her1 and her7 (her1+7) morpholino modified antisense oligonucleotides (MOs) phenocopies the b567 mutant somitic phenotype, indicating that her1 and her7 are necessary for normal somite formation and that defective somitogenesis in b567 mutant embryos is due to deletion of her1 and her7. Analysis at the cellular level indicates that somites in her1+7-deficient embryos are enlarged in the anterior-posterior dimension. Weak somite boundaries are often found within these enlarged somites which are delineated by stronger, but imperfect, boundaries. In addition, the anterior-posterior polarity of these enlarged somites is disorganized. Analysis of her1 MO-injected embryos and her7 MO-injected embryos indicates that although these genes have partially redundant functions in most of the trunk region, her1 is necessary for proper formation of the anteriormost somites and her7 is necessary for proper formation of somites posterior to somite 11. By following somite development over time, we demonstrate that her genes are necessary for the formation of alternating strong somite boundaries. Thus, even though two potential downstream components of Notch signaling are lacking in her1+7-deficient embryos, somite boundaries form, but do so with a one and a half to two segment periodicity.

Study Objective: To assess the utility of troponin I, the only molecular marker of myocardial injury not expressed in regenerating muscle, in diagnosing perioperative myocardial infarction (MI) in the setting of orthopedic surgery where false elevations in creatine kinase MB isoenzymes (CKMB) are known to occur., Design: Prospective study., Setting: University-affiliated hospital., Patients: 85 patients with risk factors for coronary artery disease (CAD) who were scheduled for orthopedic surgery, including total knee arthroplasty, 34; total hip arthroplasty, 36; posterior spine fusion, 7; and other orthopedic operations, 8., Interventions: Patients were observed in the postanesthesia care unit for at least 24 hours where they had an electrocardiogram (ECG) performed, and blood drawn to rule out MI., Measurements: Blood samples for measurement of creatine kinase MB isoenzymes (CKMB) and troponin I were drawn at 8-hour intervals for up to 24 hours., Main Results: Five (5/85) patients had elevated levels of both CKMB and troponin I postoperatively. New ECG abnormalities were present in all but one patient who had an old anterolateral MI. Troponin I peaked within 16 hours except in one patient where it continued to increase. That female patient developed cardiogenic pulmonary edema. All the others did well clinically. Six patients (6/85) had a positive CKMB index, and a negative troponin I level. None had ECG changes, except for one in whom subsequent cardiac catheterization showed insignificant CAD. They all did well clinically. All patients with an elevated troponin I level had a positive CKMB index., Conclusions: Troponin I is as sensitive a marker of MI as CKMB in the orthopedic population, but it has a higher specificity in the perioperative setting. Troponin I can be helpful in properly identifying the source of CKMB elevation postoperatively when this elevation is questionable.

Study Design: Observational analyses of 55 adult patients who underwent elective sequential anterior-posterior thoracolumbosacral surgical corrections for spinal deformities were used to evaluate the efficacy of pulmonary artery catheter monitoring., Objective: To demonstrate that during complex reconstructive surgery for spinal deformities, pulmonary artery catheter monitoring identifies a subset of patients with pulmonary injury and is essential in their management., Summary of Background Data: Patients who undergo sequential anterior-posterior thoracolumbosacral surgical corrections for spinal deformities experience significant perioperative morbidity. Although the value of pulmonary artery catheter monitoring is controversial, its use in these procedures may help identify potential physiologic complications and improve surgical outcome., Methods: All patients were monitored with a pulmonary artery catheter during surgery until at least postoperative day 1. Outcome measurements included blood loss, vertebral levels fused, operative time, postoperative respiratory complications, and days in intensive care., Results: Eight (8/55; 14.5%) patients according to pulmonary artery catheter monitoring demonstrated elevated pulmonary vascular resistance and noncardiac pulmonary edema. These patients had longer operative procedures with greater blood loss and had more postoperative respiratory complications. They were treated appropriately in intensive care and discharged without further complications., Conclusion: Pulmonary artery catheter monitoring of patients who undergo complex spinal fusion facilitates the identification of patients with pulmonary injury and is essential in the management of these patients in the postoperative period. It may, also, be a marker for embolic injury to the lung.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most widely prescribed medications worldwide and are often the first choice of treatment for acute myalgias, orthopedic injuries, postoperative pain, chronic rheumatoid arthritis, and osteoarthritis. The mechanism through which NSAIDs provide analgesia and suppress inflammation is the inhibition of the enzyme cyclooxygenase, resulting in decreased prostaglandin synthesis. The suppression of prostaglandin synthesis can also produce gastric and renal toxicity, as well as impair normal platelet function. Thus, NSAIDs are associated with potentially harmful side effects. Cyclooxygenase exists in two isoenzymatic forms, cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2). Cyclooxygenase-1 appears to be constitutively expressed in many tissues and produces prostaglandins, which regulate normal cellular functions. However, COX-2 activity is induced by proinflammatory cytokines and produces prostaglandins that mediate the inflammatory response and pain signaling transmission. Traditional nonspecific NSAIDs inhibit both COX-1 and COX-2, and in doing so, not only decrease inflammation and pain, but also promote gastrointestinal tract damage and bleeding. The potential clinical benefit of COX-2 inhibitors is significant due to the number of patients chronically treated with NSAIDs and the three- to ten-fold higher risk of gastrointestinal injury and death associated with traditional NSAIDs. Recently, a class of anti-inflammatory medications has been developed that primarily inhibits COX-2 while sparing the enzymatic activity of COX-1 at therapeutic dosages. Two medications that predominantly inhibit only COX-2, rofecoxib and celecoxib, are currently available by prescription in the United States.

Unlabelled: Perioperative myocardial ischemia (MI) is associated with postoperative cardiac morbidity. Postoperative sympatholysis may reduce the incidence of MI. This study evaluated such a reduction postoperatively with the administration of prophylactic beta-blockers in patients undergoing elective total knee arthroplasty with epidural anesthesia and postoperative epidural analgesia. One hundred seven patients were preoperatively randomized into two groups, control and beta-blockers, who received postoperative esmolol infusions on the day of surgery and metoprolol for the next 48 h to maintain a heart rate less than 80 bpm. Patients were followed for ST segment depression by using a Holter monitor and adverse cardiac outcomes. Postoperative electrocardiographic ischemia was significantly more prevalent in the control group compared with the beta-blocker group during esmolol blockade (0 of 52 vs 4 of 55; P = 0.04) and tended to be more common in the control group the next two days (8 of 55 vs 3 of 52; P = 0.135). In addition, the number of ischemic events (control, 50; beta-blockers, 16) and total ischemic time (control, 709 min; beta-blocker, 236 min) were also significantly different from the control group. Myocardial infarctions and cardiac events were more common in the control group, but these differences were not significant. Our results suggest that the use of prophylactic beta-blocker therapy may reduce the incidence of postoperative MI., Implications: Prophylactic beta adrenergic blockade administered after elective total knee arthroplasty was associated with a reduced prevalence and duration of postoperative myocardial ischemia detected with Holter monitoring.

Unlabelled: Sudden profound hypotensive and/or bradycardic events (HBE) have been reported in >20% of patients undergoing shoulder arthroscopy in the sitting position under interscalene block anesthesia. Retrospective studies suggest that the administration of beta-blockers is safe and may decrease the incidence of these episodes. We performed a randomized, prospective study to evaluate prophylaxis of these events. One hundred fifty patients were randomized to one of three groups (placebo; prophylactic metoprolol to achieve a heart rate <60 bpm or a maximal dose of 10 mg; or prophylactic glycopyrrolate to achieve a heart rate >100 bpm or a maximal dose of 6 microg/kg) immediately after the administration of the interscalene block. Blood pressure control was achieved with IV enalaprilat as needed. The incidence of HBE was 28% in the placebo group versus 5% in the metoprolol group (P = 0.004). The rate of 22% in the glycopyrrolate group was not significantly different from placebo. Preoperative heart rate and arterial blood pressure, intraoperative sedation score, IV fluids, and enalaprilat use were similar in those patients who had a HBE compared with those who did not. Many aspects of this clinical setting are similar to tilttable testing for patients with recurrent vasovagal syncope, in which beta-adrenergic blockade with metoprolol has also been shown to be effective. We conclude that the Bezold-Jarisch reflex is the most likely mechanism for these events., Implications: Episodes of acute hypotension and bradycardia occur during shoulder arthroscopy in the sitting position under interscalene block. In this study, we demonstrate that metoprolol, but not glycopyrrolate, markedly decreases the incidence of these episodes when given prophylactically immediately after the administration of the block.

Total hip arthroplasty (THA) is associated with pulmonary embolization of cement-bone marrow debris leading to cardiopulmonary complications including cardiac arrest. These complications are more prevalent during revision THA. This report assessed right ventricular function using a right ventricular ejection fraction pulmonary artery catheter (RVEF) and transesophageal echocardiography (TEE) in 18 patients undergoing revision THA. During femoral prosthesis insertion, all patients exhibited hemodynamic changes, but most of these were small and clinically insignificant. Four patients demonstrated a decrease in RVEF > or = 10% and an increase in mean pulmonary artery pressure > or = 10 mm Hg, requiring physician intervention. Two of these patients exhibited signs of pulmonary embolization postoperatively. All patients studied by TEE had detectable intracardiac emboli during femoral arthroplasty. The acute decreases in RVEF and increases in mean pulmonary artery pressures during hip arthroplasty, suggest a role for the embolization of bone marrow debris in the development of the "bone cement implantation syndrome."

Background and Objectives: Brachial plexus anesthesia is the preferred anesthetic at the authors' institution for upper extremity surgery. The article is a prospective observational evaluation of brachial plexus anesthesia for surgical success of the block and immediate and postoperative complications., Methods: Patients for upper extremity surgery (n = 508) received either an interscalene block (n = 266) or an axillary block (n = 242). Surgical anesthesia was achieved in 97% of the patients receiving an interscalene block and 93% receiving an axillary block., Results: For the interscalene block, a proximal paresthesia (shoulder) was as reliable as a more distal paresthesia (forearm, hand) for shoulder surgery. For performance of the axillary block, the transarterial approach was more successful than a single paresthesia for surgical anesthesia (96% versus 80%). Major immediate complications were infrequent, with only one mild seizure in the axillary block group and evidence of intravascular injection in only two of the patients in the interscalene block group. Many of the patients had mild paresthesias on the first day after the operation, 9% for the interscalene block and 19% for the axillary block. The incidence of postoperative neuropraxias decreased significantly by 2 weeks (interscalene block 3%, axillary block 5%), with only one patient in each group still experiencing symptoms beyond 4 weeks. In the interscalene block group, postoperative neuropraxias were associated with the site of paresthesia used for performance of the block and the use of bupivacaine., Conclusion: Both interscalene and axillary blocks are safe and effective techniques for upper extremity surgery.

Intraoperative myocardial ischemia is associated with an increased risk of a perioperative myocardial infarction (PMI) in patients undergoing coronary artery bypass graft surgery. If reversible physiologic variables could be identified that are indicators of myocardial ischemia, treatment might be instituted early to prevent cardiac morbidity. In patients undergoing elective coronary artery bypass graft surgery, we evaluated the relationship between several premorbid patient characteristics, selected hemodynamic variables, intraoperative myocardial ischemia, and a PMI. In addition we evaluated these selected hemodynamic variables as intraoperative indicators of myocardial ischemia. The following variables were evaluated: heart rate, > 80 beats/min; systolic arterial blood pressure, > 160 mm Hg; systolic arterial blood pressure, < 80 mm Hg; mean arterial blood pressure, < 60 mm Hg; pulmonary artery diastolic pressure, > 18 mm Hg; a 5 mm Hg increase in pulmonary artery diastolic pressure; rate pressure product, > 12,000 beats/min.mm Hg; and a pressure rate quotient, < 1.0 mm Hg/beats/min. The premorbid patient characteristics selected were previous myocardial infarction, recent myocardial infarction (within 1 wk of surgery), type and number of coronary lesions, beta-blocker therapy, and calcium blocker therapy. One hundred consecutive (n = 100) patients for elective coronary artery bypass graft surgery were studied prospectively before the initiation of cardiopulmonary bypass (CPB). Patients were monitored with a Hewlett Packard computer ST segment analyzer using leads II and V5. Ischemia was defined as the new onset of ST segment deviation of > or = 1 mm from the baseline electrocardiogram (ECG) (preinduction) for at least 2 min.(ABSTRACT TRUNCATED AT 250 WORDS)

Background: The pressure rate quotient (PRQ; mean arterial pressure/heart rate [MAP/HR]) less than one (PRQ < 1) has been proposed as a simple, clinically available hemodynamic index of myocardial ischemia. Recent investigations using electrocardiography (ECG) detection of myocardial ischemia have not found this index reliable. We prospectively compared PRQ < 1 to detection of myocardial ischemia via transesophageal echocardiography (TEE) and ECG in patients undergoing elective coronary artery bypass graft., Methods: Forty-six of 50 patients admitted into the study had acceptable data acquisition. Calibrated ECG leads II and V5 were recorded with a computerized ST-segment analyzer. Hemodynamic data were stored at 2-min intervals. After tracheal intubation, a 5.0-MHz TEE probe was inserted. Electrocardiography-detected ischemia was defined as new onset ST-segment deviation (> or = 1 mm) lasting for > 1 min. Transesophageal echocardiography determination of ischemia was worsening of wall motion > or = 1 grade and lasting > 1 min. PRQ < 1 was compared to ECG and/or TEE as a predictor or indicator of myocardial ischemia., Results: Electrocardiography ischemia occurred during 230 intervals in 10 patients, and in only 41 of 230 (18%) was PRQ < 1. Transesophageal echocardiography-defined ischemia occurred during 592 intervals in 9 patients, and in 119 of 592 (20%) PRQ < 1. Compared to ECG and TEE, PRQ < 1 had a low sensitivity (21%) and poor positive predictive value (25%)., Conclusions: Pressure rate quotient < 1 is an unreliable indicator and predictor of myocardial ischemia when evaluated by ECG, TEE, and the combination of these modalities in patients undergoing coronary artery bypass graft surgery.

Calcium chloride is frequently administered to patients immediately after separation from cardiopulmonary bypass to improve the contractile state of the myocardium. Animal studies suggest that calcium chloride may produce increases in pulmonary vascular resistance, which can precipitate right ventricular failure. In an attempt to determine the effect of calcium chloride administration after cardiopulmonary bypass on right ventricular function, this study was designed to evaluate patients with normal and elevated pulmonary vascular resistance. Fifty patients scheduled for elective cardiac surgery were prospectively studied for changes in ionized calcium levels before and after bypass. The impact of calcium administration on right ventricular function was assessed by a pulmonary artery catheter modified for the measurement of right ventricular ejection fraction. In all patients the level of ionized calcium decreased during bypass from a mean of 4.91 to 4.29 mg.dl-1. However, the infusion of calcium chloride (10 mg.kg-1) after bypass resulted in increasing the ionized calcium levels to prebypass levels. Administration of calcium chloride after bypass to patients with normal right ventricular function resulted in a transient increase in both cardiac output and right ventricular ejection fraction without any change in pulmonary vascular resistance. Eight patients with both elevated pulmonary vascular resistance and depressed right ventricular function were evaluated to determine the effect of calcium chloride after bypass on pulmonary vascular resistance and right ventricular ejection fraction. Administration of calcium chloride (10 mg.dl-1) to these patients did not result in any significant increase in pulmonary vascular resistance or depression of right ventricular performance. More important, in these patients, right ventricular ejection fraction and cardiac output were significantly increased after calcium chloride administration. In summary, the results of this study fail to demonstrate any increase in pulmonary vascular resistance or deterioration of right ventricular function with the administration of calcium chloride (10 mg.kg-1) after bypass in patients with elevated pulmonary vascular resistance.

Perioperative myocardial ischemia is associated with an increased risk of perioperative myocardial infarction (PMI). Several attempts have been made to define intraoperative hemodynamic predictors of myocardial ischemia. In a canine preparation with coronary stenosis, a pressure rate quotient (PRQ = mean arterial pressure/heart rate) less than one (PRQ less than 1) indicated subendocardial myocardial ischemia. The authors tested this hypothesis in patients undergoing elective coronary artery bypass graft operation (CABG), using electrocardiogram (ECG) ST-segment changes (leads II/V5) to diagnose myocardial ischemia. Sixty (n = 60) patients having CABG surgery were prospectively studied before initiation of cardiopulmonary bypass. Calibrated ECG leads II and V5 (diagnostic mode) were monitored continuously and recorded with the use of a Hewlett-Packard computer ST-segment analyzer. In addition, arterial and pulmonary artery pressures were monitored. Ischemia was defined as new-onset ST deviation (greater than or equal to 1 mm from the baseline ECG). ECG and hemodynamic data were stored at 2-min intervals for subsequent computer analysis. Serial creatinine phosphokinase (CPK) X MB (%) determinations and 12-lead ECGs were collected for the initial 3 postoperative days. Of the 3,463 intervals (2 min) available for study, 3,322 (96%) were satisfactorily recorded for 60 patients. Ischemia occurred during 65 intervals in 9 patients (9 of 60), of which only 34% (22 of 65) were associated with a PRQ less than 1 (P less than 0.01). In contrast, there were 466 intervals during which PRQ was less than 1, but without ECG evidence of ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

We tested the hypothesis that duck hepatitis B virus (DHBV) is a naturally occurring congenital infection of Pekin duck embryos. Of 219 embryos, 5-25 days after being laid, sera from 30 were found to be positive for endogenous DNA polymerase activity characteristic of hepatitis B-related viruses. The presence of the duck virus was confirmed by hybridization with cloned DHBV DNA. Viral DNA was also found in the livers of embryos incubated for 12 or 18 days. Electrophoretically different forms of DHBV DNA were identified in liver extracts that were not present in serum. These additional liver forms probably represent viral replication intermediates. These observations suggest that the vertical route is a major pathway of DHBV transmission and that viral replication may be initiated by the 12th day of embryonic life.

The major mode of natural infection of duck hepatitis B virus (DHBV) in Pekin ducks is vertical transmission, with 95 to 100% of the embryos from DHBV-infected dams eventually becoming infected. Maternally transmitted virus is present in large quantities in the yolk of unincubated eggs and is taken up by the embryo during early development. Synthesis of DHBV DNA in the embryo begins at about 6 days of incubation and coincides with the formation of the liver. DHBV DNA synthesis is incomplete, however, until 8 to 10 days of incubation, as shown by comparing the electrophoretic patterns of DHBV-specific nucleic acid species from embryonic livers at successive stages of development. From 8 days of incubation and continuing throughout embryonic development, subviral particles, which resemble viral replication intermediates isolated from infected livers of post-hatch ducklings, appear in the circulation. These particles contain a polymerase activity that utilizes an RNA template to synthesize viral DNA. Our results suggest that certain host functions, which appear during embryonic development, may be required for DHBV replication and assembly. It is possible that in mammals a similar developmental process occurs. The failure to find human hepatitis B virus in the circulation of most babies, born to hepatitis B virus carrier women, in the first few weeks after birth may reflect such a process.

The nucleosomal core histones H2A, H2B, and H3 of the chicken can be resolved by polyacrylamide gel electrophoresis in the presence of nonionic detergents into two primary structure variants each, which occur in different relative amounts in various adult tissues. Quantitative analysis of the histone components throughout embryonic development and posthatching maturation of the chicken revealed that the proportions of the three pairs of variants change independently. Thus, the two H2A variants occur in similar proportions throughout embryonic development and in all adult tissues. In contrast, only one variant each of H2B and H3 is detectable at the earliest stages (primitive streak). The second variant of these histones becomes detectable and increases gradually during somite formation (2-12 days of incubation) to reach a plateau at a level of about 3 and 10% of total H2B and H3 histones, respectively. After hatching, the relative amounts of the minor H2B and H3 variants remain at embryonic levels in those tissues which maintain a high mitotic activity such as blood-forming tissues, but increase with different kinetics in tissues which essentially stop cell division in adults (e.g., liver, kidney, etc.). However, while H2B.2 remains a very minor component in all tissues, H3.3 increases at a relatively high rate for more than a year to become the predominant H3 variant in the liver and kidney of older chickens. The changes in chicken core histone variant proportions appear to be related to changes in growth rate rather than cell differentiation. The extensive change of H3 variant proportions in nondividing adult tissues is most likely due to replication-independent incorporation of H3.3 into nucleosomes.

A small heat-stable polypeptide, ATP-dependent proteolysis factor 1 (APF-1), is an essential component of the ATP-dependent proteolytic system of rabbit reticulocytes (Ciechanover, A., Hod, Y., and Hershko. A. (1978) Biochem. Biophys. Res Commun. 81, 1100-1105). The following evidence supports the view that APF-1 is ubiquitin, a highly conserved heat-stable polypeptide found universally in nature: 1) APF-1 and ubiquitin (generously given by G. Goldstein) yield co-migrating bands on five polyacrylamide gel electrophoresis systems and in isoelectric focusing; 2) amino acid analysis shows excellent agreement between the two proteins; 3) APF-1 and ubiquitin give similar specific activity, in activating the ATP-dependent proteolysis system; 4) 125I-APF-1 and 125I-ubiquitin form electrophoretically identical covalent conjugates with endogenous reticulocyte proteins. Recently, such conjugates have been proposed as the active intermediates in ATP-dependent proteolysis (Ciechanover, A., Heller, H., Hershko, A., Haas, A.L., and Rose, I.A. (1980) Proc. Natl. Acad. Sci. U.S.A. 77, 1783-1786). Thus, ubiquitin is an essential component of the ATP-dependent system in reticulocytes and a similar role in degradation and proteolytic processing in other cells is likely.

Chicken erythrocyte histones 2A, 2B, and 3 can be resolved into nonallelic primary structure variants by polyacrylamide gel electrophoresis in the presence of Triton X-100. These variants were isolated and characterized by analysis of their tryptic and thermolytic peptides. The major variants of chicken H2A and H2B differ from the analogous component of calf thymus by a small number of conservative amino acid substitutions in the basic terminal regions, which interact with DNA. This moderate rate of allelic evolution of the slightly lysine-rich histones contrasts with the complete conservatism found in the arginine-rich histones. Chicken H4 and both chicken H3 variants are identical with their corresponding components in mammals. The amino acid substitutions distinguishing histone variants are located within the highly conserved hydrophobic regions, which are involved in histone--histone interactions.

Changes in levels of biosynthesis of DNA, RNA, and histones were compared with relative proportions of each histone class during primitive erythropoiesis in embryonic chicks. We confirmed that erythrocyte-specific histone 5 (H5) was substantial in the earliest accessible, erythroblast-enriched stage and that it doubled in relative amount between polychromatic and orthochromatic stages to about 1 mol per 2 mol of each nucleosomal histone, still considerable less than in adult definitive erythrocytes. No other histones changed during primitive erythropoiesis, but the molar proportion of histone 1 (H1) always exceeded that of H5 in these cells, unlike definitive erythrocytes. The increase in content of H5 was accompanied by continued decline in synthesis of the other histones and DNA. The accumulation of H5 during development appears to occur in steps corresponding to the maturation of the primitive and definitive erythroid cell lines. Lysine-rich histones were more easily extracted from nuclei of the erythrosynthesis in whole cells and in isolated nuclei.