Mario Moric

Perioperative Oral Pregabalin Reduces Chronic Pain After Total Knee Arthroplasty: A Prospective, Randomized, Controlled Trial

BACKGROUND: Despite the enormous success of total knee arthroplasty (TKA), chronic neuropathic pain can develop postoperatively and is both distressing and difficult to treat once established. We hypothesized that perioperative treatment with pregabalin, a chronic pain medication, would reduce the incidence of postsurgical neuropathic pain. METHODS: We performed a randomized, placebo-controlled, double-blind trial of pregabalin (300 mg) administered before TKA and for 14 days after TKA (150–50 mg twice daily). Patients were screened for the presence of neuropathic pain at 3 and 6 mo postoperatively using the Leeds Assessment of Neuropathic Symptoms and Signs scale. Secondary outcomes included postsurgical recovery and rehabilitation measures, including knee range of motion, opioid consumption, postoperative pain scores, sleep disturbance, and time to discharge as well as the occurrence of postoperative systemic complications. RESULTS: Of the 240 patients randomly assigned to the 2 treatment groups (120 in each), data for the primary outcome were obtained from 113 pregabalin patients and 115 placebo patients. At both 3 and 6 mo postoperatively, the incidence of neuropathic pain was less frequent in the pregabalin group (0%) compared with the placebo group (8.7% and 5.2% at 3 and 6 mo, respectively; P = 0.001 and P = 0.014). Patients receiving pregabalin also consumed less epidural opioids (P = 0.003), required less oral opioid pain medication while hospitalized (P = 0.005), and had greater active flexion over the first 30 postoperative days (P = 0.013). There were no differences in the actual recorded duration of hospitalization between the 2 groups, although time to achieve hospital discharge criteria was longer for placebo patients, 69.0 ± 16.0 h (mean ± sd), than that of pregabalin patients, 60.2 ± 15.8 h (P = 0.001). Sedation (P = 0.005) and confusion (P = 0.013) were more frequent on the day of surgery and postoperative day 1 in patients receiving pregabalin. CONCLUSION: Perioperative pregabalin administration reduces the incidence of chronic neuropathic pain after TKA, with less opioid consumption and better range of motion during the first 30 days of rehabilitation. However, in the doses tested, it is associated with a higher risk of early postoperative sedation and confusion.

Incidence and trends of anterior cruciate ligament reconstruction in the United States

Background: Anterior cruciate ligament (ACL) injury is among the most commonly studied injuries in orthopaedics. The previously reported incidence of ACL injury in the United States has varied considerably and is often based on expert opinion or single insurance databases. Purpose: To determine the incidence of ACL reconstruction (ACLR) in the United States; to identify changes in this incidence between 1994 and 2006; to identify changes in the demographics of ACLR over the same time period with respect to location (inpatient vs outpatient), sex, and age; and to determine the most frequent concomitant procedures performed at the time of ACLR. Study Design: Descriptive epidemiological study. Methods: International Classification of Diseases, 9th Revision (ICD-9) codes 844.2 and 717.83 were used to search the National Hospital Discharge Survey (NHDS) and the National Survey of Ambulatory Surgery (NSAS) for the diagnosis of ACL tear, and the procedure code 81.45 was used to search for ACLR. The incidence of ACLR in 1994 and 2006 was determined by use of US Census Data, and the results were then stratified based on patient age, sex, facility, concomitant diagnoses, and concomitant procedures. Results: The incidence of ACLR in the United States rose from 86,687 (95% CI, 51,844-121,530; 32.9 per 100,000 person-years) in 1994 to 129,836 (95% CI, 94,993-164,679; 43.5 per 100,000 person-years) in 2006 (P = .015). The number of ACLRs increased in patients younger than 20 years and those who were 40 years or older over this 12-year period. The incidence of ACLR in females significantly increased from 10.36 to 18.06 per 100,000 person-years between 1994 and 2006 (P = .0003), while that in males rose at a slower rate, with an incidence of 22.58 per 100,000 person-years in 1994 and 25.42 per 100,000 person-years in 2006. In 2006, 95% of ACLRs were performed in an outpatient setting, while in 1994 only 43% of ACLRs were performed in an outpatient setting. The most common concomitant procedures were partial meniscectomy and chondroplasty. Conclusion: The incidence of ACLR increased between 1994 and 2006, particularly in females as well as those younger than 20 years and those 40 years or older. Research efforts as well as cost-saving measures may be best served by targeting prevention and outcomes measures in these groups. Surgeons should be aware that concomitant injury is common.

Upregulation of prostaglandin E2 and interleukins in the central nervous system and peripheral tissue during and after surgery in humans.

Background: The central and peripheral inflammatory response to surgery may influence patient outcomes. This study examines the time course and clinical relevance of changes in prostaglandin E2 and cytokines in cerebrospinal fluid, local tissue (surgical site), and circulating blood during and after total hip replacement. Methods: Thirty osteoarthritis patients undergoing primary total hip arthroplasty with spinal anesthesia were randomly allocated to three groups (n = 10/group): placebo for 4 days before surgery and on the morning of surgery; placebo for 4 days before surgery and oral rofecoxib 50 mg on the morning of surgery; oral rofecoxib 50 mg for 4 days before surgery and the morning of surgery. Cerebrospinal fluid and plasma were collected before surgery and up to 30 h after incision for measurement of prostaglandin E2 and interleukins. When hip replacement was complete, a drain was placed in the hip wound and exudates were collected at 3 to 30 h after incision. Results: Cerebrospinal fluid showed an initial increase in interleukin 6 and a later rise in prostaglandin E2 concentration after surgery; interleukin 1&bgr; and tumor necrosis factor &agr; were undetectable. Hip surgical site fluid evidenced an increase in prostaglandin E2, interleukin 6, interleukin 8, and interleukin 1&bgr;; tumor necrosis factor &agr; decreased at 24 and 30 h. Preoperative administration of the cyclooxygenase 2 inhibitor rofecoxib reduced cerebrospinal fluid and surgical site prostaglandin E2 and cerebrospinal fluid interleukin 6. Cerebrospinal fluid prostaglandin E2 was positively correlated with postoperative pain and cerebrospinal fluid interleukin 6 with sleep disturbance. Poorer functional recovery was positively correlated with increased surgical site prostaglandin E2. Conclusions: These results suggest that upregulation of prostaglandin E2 and interleukin 6 at central sites is an important component of surgery induced inflammatory response in patients and may influence clinical outcome.

Does ACL reconstruction alter natural history?: A systematic literature review of long-term outcomes.

BACKGROUND Anterior cruciate ligament (ACL) injury can lead to tibiofemoral instability, decreased functional outcomes, and degenerative joint disease. It is unknown whether ACL reconstruction alters this progression at long-term follow-up. METHODS A systematic literature review of the long-term results (minimum follow-up, more than ten years) after operative intra-articular reconstruction of ACL injuries and after nonoperative management was performed to compare (1) knee stability on physical examination, (2) functional and patient-based outcomes, (3) the need for further surgical intervention, and (4) radiographic outcomes. After application of selection criteria, forty patient cohorts with a mean of 13.9 ± 3.1 years of postoperative follow-up were identified. Twenty-seven cohorts containing 1585 patients had undergone reconstruction, and thirteen containing 685 patients had been treated nonoperatively. RESULTS Comparison of operative and nonoperative cohorts revealed no significant differences in age, sex, body mass index, or rate of initial meniscal injury (p > 0.05 for all). Operative cohorts had significantly less need for further surgery (12.4% compared with 24.9% for nonoperative, p = 0.0176), less need for subsequent meniscal surgery (13.9% compared with 29.4%, p = 0.0017), and less decline in the Tegner score (-1.9 compared with -3.1, p = 0.0215). A difference in pivot-shift test results was observed (25.5% pivot-positive compared with 46.6% for nonoperative) but did not reach significance (p = 0.09). No significant differences were seen in outcome scores (Lysholm, International Knee Documentation Committee [IKDC], or final Tegner scores) or the rate of radiographically evident degenerative joint disease (p > 0.05 for all). CONCLUSIONS At a mean of 13.9 ± 3.1 years after injury, the patients who underwent ACL reconstruction had fewer subsequent meniscal injuries, less need for further surgery, and significantly greater improvement in activity level as measured with the Tegner score. There were no significant differences in the Lysholm score, IKDC score, or development of radiographically evident osteoarthritis.

Serum and Synovial Fluid Analysis for Diagnosing Chronic Periprosthetic Infection in Patients with Inflammatory Arthritis

BACKGROUND The serum erythrocyte sedimentation rate and C-reactive protein level, as well as the synovial fluid white blood-cell count with differential, are commonly used tests for the diagnosis of periprosthetic joint infection; however, their utility for the diagnosis of periprosthetic joint infection in patients with inflammatory arthritis is unknown. METHODS Eight hundred and three patients undergoing 871 consecutive hip and knee arthroplasties (including sixty-one in patients with inflammatory arthritis and 810 in patients with noninflammatory arthritis) were prospectively evaluated for periprosthetic joint infection. The erythrocyte sedimentation rate, C-reactive protein level, and synovial fluid white blood-cell count with differential were obtained routinely. Receiver operating characteristic curves were used to establish optimal thresholds for the diagnosis of periprosthetic joint infection, and the area under the curve was calculated to determine the overall accuracy of these tests for patients with inflammatory compared with noninflammatory arthritis. RESULTS The utility of all serum and synovial tests for predicting chronic periprosthetic joint infection was similar for patients with noninflammatory and inflammatory arthritis. The optimal cutoffs in patients with noninflammatory and inflammatory arthritis were 32 and 30 mm/hr, respectively, for the erythrocyte sedimentation rate; 15 and 17 mg/L, respectively, for the C-reactive protein level; 3450/μL and 3444/μL, respectively, for the synovial fluid white blood-cell count; and 78% and 75%, respectively, for the differential. The areas under the curves were similar for the two groups (84.9% and 85.0%, respectively, for the erythrocyte sedimentation rate; 88.5% and 85.1%, respectively, for the C-reactive protein level; 94.5% and 93.8%, respectively, for the synovial fluid white blood-cell count, and 95.0% and 93.6%, respectively, for the differential). Finally, the sensitivities, specificities, negative predictive values, and positive predictive values for all tests were also comparable in both groups. The rate of periprosthetic joint infection was significantly higher following procedures in patients with inflammatory arthritis than following procedures in patients with noninflammatory arthritis (31% compared with 18%; p = 0.013). CONCLUSIONS The erythrocyte sedimentation rate, C-reactive protein level, and synovial fluid white blood-cell count with differential are useful for diagnosing periprosthetic joint infection in patients with inflammatory as well as noninflammatory arthritis, with similar optimal cutoff values and overall testing performance. The synovial fluid white blood-cell count and differential performed the best for the diagnosis of periprosthetic joint infection. Physicians evaluating patients with a failed or painful total hip or knee arthroplasty should not assume that elevation of the erythrocyte sedimentation rate, C-reactive protein level, and synovial fluid white blood-cell count with differential is secondary to inflammatory arthropathy; rather, elevation of these markers may indicate periprosthetic joint infection, and further evaluation for infection is warranted.

Dilute Betadine Lavage Before Closure for the Prevention of Acute Postoperative Deep Periprosthetic Joint Infection

This study evaluated the efficacy of a dilute Betadine (Purdue Pharma, Stamford, Conn) lavage in preventing early deep postoperative infection after total hip (THA) and knee (TKA) arthroplasty. A protocol of dilute Betadine lavage (0.35%) for 3 minutes was introduced to the practice of the senior author in June 2008. A total of 1862 consecutive cases (630 THA and 1232 TKA) performed before this were compared with 688 consecutive cases (274 THA and 414 TKA) after for the occurrence of periprosthetic infections within the first 90 days postoperatively. Eighteen early postoperative infections were identified before the use of dilute Betadine lavage, and 1 since (0.97% and 0.15%, respectively; P = .04). There were no significant demographic differences between the 2 groups. Betadine lavage before wound closure may be an inexpensive, effective means of reducing acute postoperative infection after total joint arthroplasty.

A cross-sectional survey on prevalence and risk factors for persistent postsurgical pain 1 year after total hip and knee replacement.

Background and Objectives There is a paucity of large multi-institutional surveys to determine the prevalence of and risk factors for persistent pain after total hip (THR) and knee (TKR) replacements. We surveyed a variety of practices and patients and also correlated persistent pain with health-related quality-of-life outcomes. Methods From October 10, 2007, to March 15, 2010, patients who had undergone primary THR or TKR with a minimum follow-up of 1 year were identified. A previously published questionnaire to identify persistent postsurgical pain that included a 36-item Short Form Health Survey was mailed to this group. Independent risk factors for persistent pain were identified with logistic regression. Results Responses from 1030 patients who underwent surgery at some point in time between June 13, 2006, and June 24, 2009, were analyzed (32% response rate). Forty-six percent of patients reported persistent pain (38% after THR and 53% after TKR) with a median average pain score of 3 of 10 and worst pain score of 5. Independent risk factors for persistent pain were female sex (odds ratio [OR], 1.23), younger age (OR, 0.97), prior surgery on hip or knee (OR, 1.39), knee versus hip replacement (OR, 1.65), lower-quality postsurgical pain control (OR, 0.9), and presence of pain in other areas of the body (OR, 2.09). All scores in the 36-item Short Form Health Survey were worse (8%–28% decrease) in patients with persistent postsurgical pain (P < 0.001). Conclusions Persistent postsurgical pain is common after THR and TKR and is associated with reduced health-related quality of life, although our survey may be biased by the low response rate and retrospective recall bias. Nonmodifiable risk factors may lead to risk stratification. Severity of acute postoperative pain may be a modifiable risk factor.

The Effect of Dexmedetomidine on Perioperative Hemodynamics in Patients Undergoing Craniotomy

BACKGROUND: The perioperative course of patients undergoing intracranial surgery is frequently complicated by hypertensive episodes. Dexmedetomidine (DEX), an &agr;-2 adrenoreceptor agonist, is gaining popularity in neuroanesthesia, because its sympatholytic and antinociceptive properties may improve hemodynamic stability at critical moments of surgery. We designed this study to assess the efficacy of DEX in controlling hypertensive responses in patients undergoing intracranial surgery. METHODS: Patients scheduled for elective craniotomy were randomly assigned to receive either sevoflurane–opioid or sevoflurane–opioid–DEX anesthesia. Bispectral index was used to maintain a similar level of hypnosis in both groups (40–50). Opioids, sevoflurane, and vasoactive medications were titrated in a routine manner, at the discretion of the blinded anesthesiologist managing the case, to maintain systolic blood pressure (SBP) targeted within 90–130 mm Hg and heart rate (HR) between 50 and 90 bpm. Hemodynamic variables were continuously recorded and stored on a computer for analysis. Efficacy of the anesthetic technique in controlling SBP or HR is inversely proportional to the area under the curve (AUC) outside the targeted range. Areas under the curves above and below targeted ranges for SBP-time (AUCsbp mm Hg * min/h) and HR-time (bpm * min/h) were compared. Coefficient of variation was used to assess hemodynamic stability. RESULTS: Seventy-two patients were recruited for the study. Computerized records of 56 patients only were analyzed because of technical problems with data collection in 14 cases. AUCsbp for above the targeted range was significantly lower for patients in the DEX group (P = 0.044). The coefficient of variation for SBP or HR did not differ between groups. A significantly smaller proportion of patients in the DEX group required treatment with antihypertensive medications (12 of 28, 42% vs 24 of 28, 86%, P = 0.0008). The DEX group required fewer opioids in the intraoperative period, but there were no differences in the use of sevoflurane. In the postanesthesia care unit, patients in the DEX group had fewer hypertensive episodes (1.25 ± 1.55 vs 2.50 ± 2.00, P = 0.0114) and were discharged earlier (91 ± 17 vs 130 ± 27 min, P < 0.0001). There were no differences in the requirement for postoperative opioids or antiemetics. CONCLUSIONS: By using indices, which assess a global hemodynamic stability of the anesthetic, we determined that intraoperative DEX infusion was effective for blunting the increases in SBP perioperatively. The use of DEX did not increase the incidence of hypotension or bradycardia, common side effects of the drug.

Local anesthetic sciatic nerve block and nerve fiber damage in diabetic rats

Background and Objectives: A concern for anesthesiologists is whether local anesthetics are more toxic to peripheral nerves in diabetic patients. A previous study in streptozotocin-induced diabetic rats showed that larger doses of lidocaine produce moderate nerve injury after nerve block in normal rats and worse injury in diabetic rats. However, it is not clear whether a smaller local anesthetic dose that produces negligible nerve fiber damage in normal rats will produce significant nerve damage in diabetic rats and if adding adjuvant drugs modulates this effect. Methods: Rats were intravenously injected with 50 mg/kg streptozotocin to induce diabetes (blood glucose levels >250 mg/dL) and diabetic neuropathy. After waiting 35 days, an injection (0.1 mL) of 1% lidocaine alone, or with 5 &mgr;g/mL epinephrine or 7.5 &mgr;g/mL clonidine added, or 0.5% ropivacaine alone was performed at the left sciatic notch in both diabetic and nondiabetic rats. The duration of sensory (pin prick) and motor (toe spreading reflex) nerve block in the hind paws was determined. For histologic controls, all rats also received saline vehicle injection into the right sciatic notch. Another group of uninjected rats was used as naive controls. Left and right nerves were removed 2 days after injection and fixed in situ with a 4% glutaraldehyde solution. Myelinated axon profiles suggestive of neuropathy (myelin figures, pale and swollen, or dark-staining axoplasm) were counted and expressed as a percentage of the total number of fibers in each rat sciatic nerve. Results: All streptozotocin-injected rats became diabetic and had pronounced tactile allodynia. All rats had sensory and motor nerve blocks lasting for at least 50 mins after injection of local anesthetic. The duration of sensory and motor nerve block was longer in diabetic rats than in nondiabetic rats for all drug groups tested. None of the sciatic nerves examined showed greater than 3% nerve fiber degeneration. Although lidocaine in diabetic rats did not produce nerve fiber damage, diabetic rats receiving lidocaine/clonidine or ropivacaine had more abnormal myelinated axon profiles than did nondiabetic rats receiving the same drug. Conclusions: The duration of sciatic nerve block with local anesthetics is longer in diabetic compared with nondiabetic rats. A small, but statistically significant, increase in nerve damage occurred in diabetic rats after nerve block with ropivacaine alone or when duration of lidocaine block was extended with clonidine. These findings may have implications for dosing of local anesthetics in diabetic patients undergoing regional analgesia with nerve blocks.

Peripheral nerve stimulator for the treatment of supraorbital neuralgia : a retrospective case series

Peripheral nerve blocks of the supraorbital, supratrochlear or occipital nerve have been utilized for the relief of headaches, although relief may be short-lasting. The purpose of this study was to evaluate the efficacy of supraorbital nerve stimulation for treatment of intractable supraorbital neuralgia. Patients presenting to the pain clinic with refractory frontal headaches who responded to a diagnostic supraorbital nerve block were selected for this case series. Patients underwent a trial of supraorbital nerve stimulation, and efficacy was assessed after 5-7 days (n = 16). From the trial, 10 patients consented to undergo permanent implantation of the stimulator. Opioid consumption and headache scores were monitored preoperatively and at timed intervals for 30 weeks. Headache scores decreased, and opioid consumption was reduced in half, and these beneficial accomplishments were maintained up to 30 weeks after implantation. In selected patients, supraorbital nerve stimulation for the treatment of chronic frontal headaches appears to be efficacious.