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.

Pain following battlefield injury and evacuation: a survey of 110 casualties from the wars in Iraq and Afghanistan.

OBJECTIVE: Advances in regional anesthesia, specifically continuous peripheral nerve blocks (CPNBs), have greatly improved pain outcomes for wounded soldiers in Iraq and Afghanistan. pain management practice variations, however, do exist, depending on the availability of pain-trained military professionals deployed to combat support hospitals. an exploratory study was undertaken to examine pain and other outcomes during evacuation and at landstuhl regional medical center (lrmc), germany. DESIGN: a mixed-methods, semistructured interview survey design was conducted on a convenience sample of wounded u.s. soldiers evacuated from iraq and afghanistan to lrmc. setting and patients. a total of 110 wounded soldiers evacuated from IRAQ and Afghanistan from July 2007 to February 2008 completed a pain survey at LRMC. Data were collected on demographics, injury mechanism, last 24-hour average, least, and worst, and pain now by using a 0-10 scale, and percent pain relief (from 0% [No relief] to 100% [Complete relief]). Similar items and measures of anxiety, distress, and worry during flight transport were measured (from 0 [None] to 10 [Extreme]). Responses were analyzed by using descriptive and correlational statistics, multiple linear regression, Mann-Whitney U-tests, and t-tests. The Walter Reed Army Medical Center, Human Use Committee approved this investigation. RESULTS: Participants were typically male (99.1%), Caucasian (80%), and injured from improvised explosive devices (60%) and gunshots (21.8%). Average and worst pain scores were inversely correlated with pain relief during transport (r = -0.58 and r = -0.46, respectively; P < 0.001), and low to moderately positively correlated with increased anxiety, distress, and worry during transport (P < 0.05). Average percent pain relief achieved was 45.2% +/- 26.6% during transport and 64.5% +/- 23.5% while at LRMC (P < 0.001). Participants with CPNB catheters placed at LRMC reported significantly less pain right now (P = 0.031) and better pain relief (P = 0.029) than soldiers without CPNBs. CONCLUSIONS: Our findings underscore the value of early aggressive pain management after major combat injuries. Increased pain was associated with increased anxiety, distress, and worry during transport, suggesting the need for psychological management along with analgesia. Regional anesthesia techniques while at LRMC contributed to better pain outcomes.

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.

Continuous peripheral nerve block for battlefield anesthesia and evacuation.

Peripheral nerve and continuous peripheral nerve block (CPNB) have the potential to be valuable techniques in combat anesthesia. We describe the first successful application of CPNB in the pain management and surgical management of a combat casualty as he was evacuated from the Iraqi battlefield to the United States.

An intravenous ketamine test as a predictive response tool in opioid-exposed patients with persistent pain.

Chronic pain patients who are treated with opioid therapy represent a significant challenge to medical professionals. When pain recurs in the face of a previously effective opioid regimen, treatment options include dose escalation, opioid rotation, drug holidays, and the addition of adjuvants. Some experts advocate the use of N-methyl-D-aspartate receptor (NMDA-R) antagonists to combat tolerance. Recently, the use of an intravenous (i.v.) ketamine infusion to predict the response to a dextromethorphan (DX) treatment trial has been described. In this study, 56 opioid-exposed patients with recurrent pain were treated with a low-dose (0.1mg/kg) i.v. ketamine test followed by a DX treatment course. Using previously designated cutoff values for a positive response to ketamine (67% or more pain relief) and DX (50% or more pain relief), the sensitivity, specificity, positive predictive value, and negative predictive value for an i.v. ketamine infusion to predict subsequent response to DX treatment were 72%, 68%, 52%, and 85%, respectively. The observed agreement between analgesic responses was 78%, indicating a highly significant correlation (r=0.54, P=0.0001). Subgroup classification revealed no significant differences in the response to either ketamine or DX treatment based on pain classification (i.e., nociceptive, neuropathic, or mixed) or placebo response. In contrast, a weaker correlation between ketamine and DX response was found in subjects requiring high-dose rather than low-dose opioid therapy. A significant correlation also was noted between the development of side effects for the two NMDA-R antagonists. Based on these results, we conclude that an i.v. ketamine test may be a valuable tool in predicting subsequent response to DX treatment in opioid-exposed patients. with persistent pain.

Responding to challenges in modern combat casualty care: innovative use of advanced regional anesthesia.

BACKGROUND: The war in Iraq has resulted in a high incidence of severe extremity injury requiring multiple surgical procedures and extensive rehabilitation. We describe the use of advanced regional anesthesia to meet this significant medical challenge. METHODS: From March 2003 to December 2004, 4,100 casualties have been evacuated to Walter Reed Army Medical Center (WRAMC). Of 1,400 inpatients, 750 have been battle-injured with 500 having extremity injuries. Of these, 287 (57%) received surgical care incorporating regional anesthesia including single-injection peripheral nerve blocks and continuous peripheral and epidural infusion catheters. Wounding, surgical, anesthetic, and outcomes data have been prospectively collected. RESULTS: Over 900 operations (mean 4+/-2/patient) were performed on 287 casualties prior to arrival at WRAMC, and 634 operations (mean 2+/-1/patient) were performed at WRAMC. Thirty-five percent of this cohort was amputees. In the study group, 646 advanced regional anesthesia procedures, including 361 continuous peripheral nerve blocks (CPNBs), were performed with a mean catheter infusion time of 9 days (1-34). Catheter-related complications occurred in 11.9% of casualties and were technical or minor in nature. Catheter-related infection rate was 1.9%. In 126 casualties with indwelling CPNB catheters, a significant decrease in pain score over 7 days was apparent (mean 3.7+/-0.2 to 2.2+/-0.2, P<0.001). CONCLUSION: Advanced regional anesthetic techniques allowed for safe perioperative surgical anesthesia and analgesia in the management of the modern combat casualty.