Pregabalin and pain after total knee arthroplasty: a double-blind, randomized, placebo-controlled, multidose trial.

BACKGROUND: Pregabalin may reduce postoperative pain and opioid use. Higher doses may be more effective, but may cause sedation and confusion. This prospective, randomized, blinded, placebo-controlled study tested the hypothesis that pregabalin reduces pain at 2 weeks after total knee arthroplasty, but increases drowsiness and confusion. METHODS: Patients (30 per group) received capsules containing pregabalin (0, 50, 100, or 150 mg); two capsules before surgery, one capsule twice a day until postoperative day (POD) 14, one on POD15, and one on POD16. Multimodal analgesia included femoral nerve block, epidural analgesia, oxycodone-paracetamol, and meloxicam. The primary outcome was pain with flexion (POD14). RESULTS: Pregabalin did not reduce pain at rest, with ambulation, or with flexion at 2 weeks (P=0.69, 0.23, and 0.90, respectively). Pregabalin increased POD1 drowsiness (34.5, 37.9, 55.2, and 58.6% in the 0, 50, 100, and 150 mg arms, respectively; P=0.030), but did not increase confusion (0, 3.5, 0, and 3.5%, respectively; P=0.75). Pregabalin had no effect on acute or chronic pain, opioid consumption, or analgesic side-effects. Pregabalin reduced POD14 patient satisfaction [1-10 scale, median (first quartile, third quartile): 9 (8, 10), 8 (7, 10), 8 (5, 9), and 8 (6, 9.3), respectively; P=0.023). Protocol compliance was 63% by POD14 (50.0, 70.0, 76.7, and 56.7% compliance, respectively), with no effect of dose on compliance. Per-protocol analysis of compliant patients showed no effect of pregabalin on pain scores. CONCLUSIONS: Pregabalin had no beneficial effects, but increased sedation and decreased patient satisfaction. This study does not support routine perioperative pregabalin for total knee arthroplasty patients. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: http://www.clinicaltrials.gov/ct2/show/study/NCT01333956.

Meningitis or epidural abscesses after neuraxial block for removal of infected hip or knee prostheses.

BACKGROUND: Infection, whether localized or systemic, can be a relative contraindication to neuraxial anaesthesia. Data correlating neuraxial anaesthesia and the development of meningitis or epidural abscess in this setting are limited. METHODS: Retrospective chart review was performed on 710 medical records of patients admitted between 1998 and 2009 for removal of potentially infected total hip and total knee prostheses. Ultimately, 474 patients were identified as being infected. Factors that predisposed a patient to an immunocompromised state, and signs and symptoms of infection in the pre-, intra-, and postoperative stages were documented. Bacteraemic patients were reviewed for signs of neuraxial infection. The endpoint of follow-up was development of complications before hospital discharge. RESULTS: All 474 patients had removal of the infected prosthesis under neuraxial anaesthesia. Mean patient age was 65.5 yr (58% >65 yr) and mean length of hospital stay was 21 days. Patient characteristics included concurrent disease (65%), steroid use (5.3%), preoperative antibiotic use (50.8%), signs of inflammatory process (84%), bacteraemia (4.2%), and documented positive intraoperative joint cultures (88%). Using clinical standards for diagnosis of central neuraxial infection, patients developed infectious complications (incidence of 0.6% on 95% confidence interval), although three patients had findings attributable to anaesthesia, including epidural haematoma, psoas abscess, and back pain. CONCLUSIONS: Based on clinical criteria, our findings suggest that the incidence of central nervous system infection after neuraxial anaesthesia in patients with infected hip and knee prostheses is low after neuraxial block.

The one year incidence of postoperative myocardial infarction in an orthopedic population.

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.

Troponin I as a diagnostic marker of a perioperative myocardial infarction in the orthopedic population.

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.

Lung transplantation for chemotherapy-induced pulmonary fibrosis.

A 26-year-old man cured of childhood acute lymphoblastic leukemia underwent a single lung transplant for drug-induced pulmonary toxicity 9 years after the completion of chemotherapy. It is not known whether patients cured of a malignancy who undergo organ transplantation are at increased risk of malignancy as compared to other organ transplant recipients. There was no evidence of recurrent or secondary malignancy in this case. Since single lung transplantation has been effective for idiopathic pulmonary fibrosis, it should be considered for patients cured of a malignancy who develop chemotherapy-induced pulmonary fibrosis.

Pulmonary complications in lymphoma patients treated with high-dose therapy autologous bone marrow transplantation.

To define the incidence and spectrum of pulmonary complications following autologous bone marrow transplantation (BMT), we retrospectively reviewed the course of 77 consecutive patients with Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) who failed conventional therapy and underwent autologous BMT. Forty-five percent of the 77 patients developed respiratory complications with a mortality from pulmonary causes of 26%. A total of 38 episodes of respiratory compromise occurred in 35 patients. Infections accounted for 15 episodes (39%) and included bacterial (16%), Aspergillus (8%) cytomegalovirus (8%), Herpes simplex (3%), and other (5%) pneumonias. The spectrum of infections was similar to that reported following allogeneic BMT, but cytomegalovirus pneumonia was not as frequent a problem in those with autologous transplant. Mortality from pulmonary infections was 33%. Noninfectious disorders accounted for 23 episodes (61%) and included recurrent HD (18%), radiation/drug toxicity (16%), and acute respiratory failure thought secondary to pulmonary alveolar hemorrhage (26%). This latter entity developed acutely within 2 wk following BMT and was associated with use of thoracic radiation for treatment of malignant disease in the chest just prior to BMT (p < 0.05). It was not associated with the age of the patient or presence of thrombocytopenia, coagulopathy, renal insufficiency or neutropenia (p NS). Mortality from noninfectious causes was 65%, but in those with pulmonary hemorrhage it was 100%. In conclusion, pulmonary complications are a major source of morbidity and mortality in patients with HD and NHL undergoing autologous BMT.(ABSTRACT TRUNCATED AT 250 WORDS)

Aerosolized pentamidine: effect on diagnosis and presentation of Pneumocystis carinii pneumonia.

STUDY OBJECTIVE: To determine the effect of previous aerosolized pentamidine therapy on diagnosis and presentation of Pneumocystis carinii pneumonia. DESIGN: A retrospective study. SETTING: A tertiary care hospital. PATIENTS: Fifty-two consecutive patients with P. carinii pneumonia and underlying infection with the human immunodeficiency virus (HIV) who had bronchoscopy. Twenty-one patients who were on aerosolized pentamidine therapy served as the study group. Thirty-one patients who had not received the drug served as the control group. MEASUREMENTS AND MAIN RESULTS: The yield of bronchoalveolar lavage for P. carinii pneumonia was 62% for the study group and 100% for the control group (P less than 0.05). This lower yield was significant for the subset of patients having their first episode of P. carinii pneumonia. The yield of transbronchial biopsy was similar for both groups of patients (81% compared with 84%). The yield of bronchoscopy was not influenced by use of zidovudine. Review of lavage specimen slides suggested that there may be fewer organisms present in patients receiving aerosolized pentamidine. An atypical roentgenographic presentation of upper lobe predominant infiltrates was seen in 38% of the study patients and 7% of the control patients. In addition, pneumothoraces and cystic changes were also frequently seen in the study patients. Gallium scans, when done, were also atypical in the study group. Markers of the severity of disease, however, were similar in both groups. CONCLUSION: The yield of bronchoalveolar lavage for P. carinii pneumonia in HIV-infected patients is lower in patients receiving aerosolized pentamidine. Unusual roentgenographic presentations and atypical gallium scans are also found in this setting.

Bleomycin-induced pulmonary toxicity.

Bleomycin is recognized to cause an interstitial pneumonitis that can lead to fibrosis. Although its occurrence may be sporadic, some factors may increase the risk of such a pulmonary reaction. In this article the clinical setting and presentation, radiographic manifestations, pathologic findings, and the prognosis of bleomycin-induced interstitial fibrosis are described. Additionally, the role of pulmonary function tests in monitoring patients for toxicity is discussed.

Cytomegalovirus pneumonia after bone marrow transplantation successfully treated with the combination of ganciclovir and high-dose intravenous immune globulin.

STUDY OBJECTIVE: To assess the efficacy of the combination of the antiviral agent ganciclovir (9-1,3 dihydroxy-2-propoxymethylguanine) and high-dose intravenous immune globulin for treating cytomegalovirus interstitial pneumonitis after allogeneic bone marrow transplantation. DESIGN: Nonrandomized prospective trial of combined treatment with two drugs; findings in these patients were compared with those in control patients treated with either of the two drugs alone. SETTING: Medical, pediatric, and intensive care units of a tertiary-care cancer treatment center. PATIENTS: Consecutive cases of 10 patients in the study group and of 11 patients in a historical control group with evidence of cytomegalovirus pneumonia after bone marrow transplantation for treatment of leukemia or congenital immune deficiency. INTERVENTIONS: Study Group (10 patients): ganciclovir, 2.5 mg/kg body weight, three times daily for 20 days, plus intravenous immune globulin, 500 mg/kg every other day for ten doses. Patients were then given ganciclovir, 5 mg/kg.d three to five times a week for 20 more doses, and intravenous immune globulin, 500 mg/kg twice a week for 8 more doses. Control Group (11 patients): ganciclovir alone (2 patients), 5 mg/kg twice a day for 14 to 21 days; cytomegalovirus hyperimmune globulin (5 patients), 400 mg/kg.d for 10 days; and intravenous immune globulin (4 patients), 400 mg/kg.d for 10 days. MEASUREMENTS AND MAIN RESULTS: Responses were observed in all patients treated with combination therapy; 7 of 10 patients were alive and well, and had no recurrence of disease at a median of 10 months after therapy. No therapeutic benefit was observed, and none of the 11 patients treated with either ganciclovir or intravenous immune globulin alone survived (P = 0.001 by Fisher exact test). CONCLUSIONS: Ganciclovir, when combined with high-dose intravenous immune globulin, appears to have significantly altered the outcome of patients with cytomegalovirus pneumonia after allogeneic bone marrow transplantation.