Effects of low-dose IV ketamine on peripheral and central pain from major limb injuries sustained in combat.

OBJECTIVE: Examine response patterns to low-dose intravenous (IV) ketamine continuous infusions on multiple pain outcomes, and demonstrate effectiveness, safety, and tolerability of ketamine administration on general wards. DESIGN: Retrospective case series of consecutive patients given low-dose IV ketamine continuous infusions. SETTING: Walter Reed Army Medical Center, Washington, DC. PATIENTS: Nineteen eligible inpatients with neuropathic pain from major limb injuries sustained in combat with inadequate pain control from multimodal analgesia. INTERVENTIONS: A 3-day IV infusion of ketamine at doses ≤ 120 µg/kg/h. OUTCOME MEASURES: Daily present (PPI), average (API), and worst (WPI) pain intensity (0-10), global pain relief (GPR) (1 "no relief" to 5 "complete relief"), daily assessments of adverse events, and daily opioid requirements measured during therapy. RESULTS: A significant reduction in PPI (P < 0.001) and improvement in GPR (P = 0.031) was noted over time. Higher baseline WPI (≥ 7; N = 4) was associated with a significant decrease in WPI (P = 0.0388), but lower baseline WPI (N = 5) was not. Significant mean percent decreases in PPI with higher baseline PPI (N = 8; P = 0.0078) and WPI with no phantom limb pain (PLP) (N = 10; P = 0.0436) were observed. Mean percent increase in overall GPR was better for those reporting GPR scores ≤ 3 (N = 13) in the first 24 hours of therapy (P = 0.0153). While not significant, mean opioid requirement (IV morphine equivalents) decreased from 129.9 mgs ± 137.3 on day 1 to 112.14 ± 86.3 24 hours after therapy. CONCLUSIONS: Low-dose ketamine infusions for complex combat injury pain were safe and effective, and demonstrated response patterns over time and by baseline pain score stratification and presence or absence of PLP.

The effect of lipid emulsion infusion on postmortem ropivacaine concentrations in swine: endeavoring to comprehend a soldier's death.

BACKGROUND: Lipid emulsion (20%) is advocated as a rescue drug for local anesthetic toxicity. No study has measured the impact of lipid emulsion therapy on postmortem local anesthetic serum levels. METHODS: We anesthetized Yorkshire swine (n = 11) and standard monitors were placed. The swine received 1.5 mg/kg/min IV ropivacaine until death (asystole). Blood samples were drawn before infusion (baseline) and at 5-minute intervals during the infusion for measurement of blood gases and free, bound, and total serum ropivacaine concentrations via high-performance liquid chromatography. Five swine received ropivacaine only, and 6 swine received ropivacaine plus a single bolus dose of 20% lipid emulsion (1 mg/kg) when the mean arterial blood pressure reached 50 mm Hg. Ropivacaine infusions were terminated at asystole and no resuscitation was initiated. Total ropivacaine dose and time to death were recorded. The swine were cooled (mean temperature, 25.5°C ± 0.8°C at 6 hours postmortem) to reflect morgue conditions. Serum samples were drawn at asystole, 1, 3, and 6 hours postmortem for analysis. Additionally, a craniotomy and laparotomy were performed at those times to remove 1.5 to 3 g each of brain, lung, liver, kidney, and muscle for analysis. RESULTS: Analysis of the postmortem serum ropivacaine concentrations in the control and the lipid-treated animals indicated that both the total (bound and not bound to proteins) and free (not bound to proteins) ropivacaine concentrations were significantly higher in the lipid-treated animals (P = 0.0094 and P = 0.0063, respectively). Furthermore, time had a significant effect on increasing the postmortem free ropivacaine concentrations (P = 0.0095). The lipid group had a statistically significant earlier onset of death (asystole) compared with the control group (P = 0.0274). Tissue analysis indicated that the ropivacaine concentration significantly decreased postmortem in the lung, kidney, and brain tissues of the lipid-treated animals (P = 0.0168, P = 0.0073, and P = 0.0018, respectively). Tissue drug concentrations in the control animals remained unchanged after death. CONCLUSIONS: Our data show that postmortem blood samples in swine that experience local anesthetic cardiovascular collapse and are treated with lipid emulsions will result in measurements that cannot be directly extrapolated to premortem drug concentrations.

Serum ropivacaine concentrations and systemic local anesthetic toxicity in trauma patients receiving long-term continuous peripheral nerve block catheters.

BACKGROUND: Ropivacaine is a long-acting local anesthetic used frequently for peripheral nerve blocks and continuous peripheral nerve block catheters. Combat trauma patients at Walter Reed Army Medical Center often receive continuous peripheral nerve block catheters as part of their pain regimen. These catheters remain in situ for several days to weeks. In this study, we evaluated the free ropivacaine drug levels over time in trauma patients by measuring the serum concentration of bound and unbound local anesthetic. The corresponding alpha(1)-acid glycoprotein concentration in patients with prolonged ropivacaine infusions was also measured. METHODS: Fifteen patients were enrolled in the study; 2 patients were excluded because only a single ropivacaine level was obtained. Of the remaining 13 patients in the study, 2 had peripheral nerve catheters placed at the time of enrollment; the remaining 11 patients had catheters placed before enrollment. These patients were already receiving 0.2% ropivacaine infusions for a period of 18-126 h before the first assessment of local anesthetic level. Catheters infused 0.2% ropivacaine at a rate of 6-14 mL/h; catheter boluses were administered with 0.5% ropivacaine. Local anesthetic blood concentrations were scheduled to be measured on Days 1, 3, 5, 7, and 10 and every 3 days thereafter until all catheters were removed, although not all patients underwent each assessment. Specimens were assayed using high-performance liquid chromatography for total and free serum ropivacaine concentrations. Alpha(1)-acid glycoprotein was also measured. RESULTS: Thirteen patients remained in the study, for a total of 59 blood samples. The median number of days catheters remained in situ for the duration of acute pain therapy was 7 days (range: 6-27 days). The median number of days catheters remained in situ after enrollment into the study was 7 days (range: 4-25 days). The median number of blood samples collected per patient was 4 (range: 2-10 samples). Two patients had isolated increased concentrations of free ropivacaine into a previously identified toxic range with no obvious mitigating factors; both patients had received a 300-mg bolus of 0.5% ropivacaine approximately 24 h before that blood collection. The median ropivacaine concentration over the length of the study was 0.11 mg/L (range: undetectable to 0.63 mg/L). During the first week of the study, the median change in ropivacaine concentration per patient was 0.00 mg/L (range: -0.35 to 0.47 mg/L). CONCLUSION: Although 2 patients demonstrated isolated serum ropivacaine concentration spikes into a previously identified toxic range, continuous peripheral nerve block catheter management and local anesthetic doses as practiced at Walter Reed Army Medical Center did not result in clinically evident systemic ropivacaine toxicity. There was no correlation between free ropivacaine concentration and alpha(1)-acid glycoprotein concentration except in patients who had already been receiving ropivacaine infusions before entering the study. Despite this lack of correlation, the total duration of local anesthetic infusion did not seem to influence the free concentration of the drug.

Double-blinded, placebo-controlled, prospective randomized trial evaluating the efficacy of paravertebral block with and without continuous paravertebral block analgesia in outpatient breast cancer surgery.

BACKGROUND: Paravertebral block (PVB) is an effective alternative to general anesthesia for breast cancer surgery. Continuous paravertebral block (CPVB) anesthesia may extend postoperative analgesia at home and improve quality of early postoperative recovery of breast cancer patients. PURPOSE: This double-blinded randomized trial was conducted to compare degree of pain, nausea, mood, level of symptom distress, and time to return to normal daily activity between PVB and PVB + CPVB in patients undergoing outpatient breast cancer surgery. PATIENTS AND METHODS: Between July 2003 and April 2008 we randomly assigned 94 (73 evaluable) patients in a 1:1:1 ratio with early breast cancer to single injection PVB followed by CPVB infusion of 0.1% or 0.2% ropivacaine vs placebo (saline) for 48 hours postoperatively for unilateral breast cancer surgery without reconstruction. The primary study endpoint was the degree of pain, nausea, mood state, level of symptom distress, and recovery time. RESULTS: Of the 468 patients assessed for eligibility, 94 consented and 21 with incomplete data or follow-up were excluded, leaving 73 subjects for analysis. There was no clinically significant difference in degree of postoperative pain, nausea, mood state, level of symptom distress, or return to normal activity among the three study groups. CONCLUSION: The current study does not support the routine use of continuous paravertebral catheter anesthesia in patients undergoing operative treatment for breast cancer.

Standard versus pH-adjusted and lidocaine supplemented radiocolloid for patients undergoing sentinel-lymph-node mapping and biopsy for early breast cancer (PASSION-P trial): a double-blind, randomised controlled trial.

BACKGROUND: Sentinel-lymph-node (SLN) mapping and biopsy maintains staging accuracy in early breast cancer and identifies patients for selective lymphadenectomy. SLN mapping requires injection of technetium-99m-sulfur colloid-an effective but sometimes painful method, for which better pain-management strategies are needed. In this randomised, double-blind trial, we compared degree of pain between standard radiocolloid injection and pH-adjusted and lidocaine-supplemented formulations for patients undergoing SLN mapping for breast cancer. METHODS: Between Jan 13, 2006, and April 30, 2009, 140 patients with early breast cancer were randomly assigned in a 1:1:1:1 fashion to receive the standard topical 4% lidocaine cream and injection of [(99m)Tc]Tc-sulfur colloid (n=35), or to one of three other study groups: topical placebo cream and injection of Tc-sulfur colloid containing either sodium bicarbonate (n=35), 1% lidocaine (n=35), or sodium bicarbonate and 1% lidocaine (n=35). The randomisation sequence was computer generated, and all patients and investigators were masked to treatment allocation. The primary endpoint was patient-reported breast pain immediately after radioisotope injection, using the Wong-Baker FACES pain rating scale and McGill pain questionnaire, analysed in the per-protocol population. This study is registered with ClinicalTrials.gov, number NCT00940199. FINDINGS: 19 of the 140 patients enrolled were excluded from analysis: nine declined study participation or sought care elsewhere, nine did not undergo SLN mapping because of disease extent or a technical problem, and one had unreliable data. There were no adverse events. Mean pain scores on the Wong-Baker scale (0-10) were: 6.0 (SD 2.6) for those who received standard of practice, 4.7 (3.0) for those who received radiocolloid plus bicarbonate, 1.6 (1.4) for those who received radiocolloid plus 1% lidocaine, and 1.6 (1.3) for those who received radiocolloid plus bicarbonate and 1% lidocaine (p<0.0001). Mean pain rating, according to the McGill questionnaire (0-78), was 17.5 (SD 11.8) for the standard-of-care group, 15.4 (14.4) for the sodium bicarbonate group, 4.6 (4.5) for the 1% lidocaine group, and 3.4 (5.1) for the sodium bicarbonate plus 1% lidocaine group (p<0.0001). SLN identification rates for each group were: 96% for the standard of care, 97% for sodium bicarbonate, 90% for 1% lidocaine, and 90% for sodium bicarbonate plus 1% lidocaine group (p=0.56). INTERPRETATION: For centres that use radiocolloid injections for SLN mapping in patients with early breast cancer, the addition of 1% lidocaine to the radioisotope solution can improve patient comfort, without compromising SLN identification. FUNDING: US Military Cancer Institute, the Clinical Breast Care Project, and the Army Regional Anesthesia and Pain Management Initiative.

Advanced regional anesthesia morbidity and mortality grading system: regional anesthesia outcomes reporting (ROAR).

OBJECTIVE: A regional anesthesia complication grading system (regional anesthesia outcomes reporting [ROAR]) was developed and applied to 1,213 consecutive patients over a 14-month period. The goal of the project was the creation of a system to standardize complication reporting in the regional anesthesia literature. DESIGN: Patient demographics, status as a war casualty, regional block procedure-specific details, and complication grade were entered into an Internet-based, encrypted Department of Defense database. Regional anesthesia complications were later graded and subcategorized depending on what phase of the block the procedural adverse event took place. RESULTS: One thousand ninety-eight (90.5%) patients had neither regional anesthesia associated technical difficulties or more severe complications. Of a total of 147 cases with adverse events among 115 patients (1.3 per patient), the majority (63.3%, 93/147) were low-grade complications resulting in no significant morbidity. The most common complications resulting in patient morbidity were failed block requiring catheter removal and/or supplemental block (35.4%, 17/48). High grade complications represented only 4.1% (6/147) of all peri-procedural morbidity. These complications included pneumothorax requiring tube thoracostomy, transient laryngeal nerve dysfunction, and cancellation of planned operation after peripheral nerve block or catheter placement. CONCLUSIONS: The value of the ROAR system is that it identifies important issues in risk management in regional anesthesia, thereby providing opportunities for further investigation and clinical practice refinement. Furthermore, it provides for a common language when reporting outcomes in the regional anesthesia literature. Use of the ROAR system will provide consistency in outcomes reporting and facilitate comparisons between methods and procedures.