Intraoperative Blood Pressure Monitoring in Obese Patients.

BACKGROUND: The optimal method for blood pressure monitoring in obese surgical patients remains unknown. Arterial catheters can cause potential complications, and noninvasive oscillometry provides only intermittent values. Finger cuff methods allow continuous noninvasive monitoring. The authors tested the hypothesis that the agreement between finger cuff and intraarterial measurements is better than the agreement between oscillometric and intraarterial measurements. METHODS: This prospective study compared intraarterial (reference method), finger cuff, and oscillometric (upper arm, forearm, and lower leg) blood pressure measurements in 90 obese patients having bariatric surgery using Bland-Altman analysis, four-quadrant plot and concordance analysis (to assess the ability of monitoring methods to follow blood pressure changes), and error grid analysis (to describe the clinical relevance of measurement differences). RESULTS: The difference (mean ± SD) between finger cuff and intraarterial measurements was -1 mmHg (± 11 mmHg) for mean arterial pressure, -7 mmHg (± 14 mmHg) for systolic blood pressure, and 0 mmHg (± 11 mmHg) for diastolic blood pressure. Concordance between changes in finger cuff and intraarterial measurements was 88% (mean arterial pressure), 85% (systolic blood pressure), and 81% (diastolic blood pressure). In error grid analysis comparing finger cuff and intraarterial measurements, the proportions of measurements in risk zones A to E were 77.1%, 21.6%, 0.9%, 0.4%, and 0.0% for mean arterial pressure, respectively, and 89.5%, 9.8%, 0.2%, 0.4%, and 0.2%, respectively, for systolic blood pressure. For mean arterial pressure and diastolic blood pressure, absolute agreement and trending agreement between finger cuff and intraarterial measurements were better than between oscillometric (at each of the three measurement sites) and intraarterial measurements. Forearm performed better than upper arm and lower leg monitoring with regard to absolute agreement and trending agreement with intraarterial monitoring. CONCLUSIONS: The agreement between finger cuff and intraarterial measurements was better than the agreement between oscillometric and intraarterial measurements for mean arterial pressure and diastolic blood pressure in obese patients during surgery. Forearm oscillometry exhibits better measurement performance than upper arm or lower leg oscillometry.

Non-invasive measurement of pulse pressure variation using a finger-cuff method in obese patients having laparoscopic bariatric surgery.

Pulse pressure variation (PPV) is a dynamic cardiac preload variable used to predict fluid responsiveness. PPV can be measured non-invasively using innovative finger-cuff systems allowing for continuous arterial pressure waveform recording, e.g., the Nexfin system [BMEYE B.V., Amsterdam, The Netherlands; now Clearsight (Edwards Lifesciences, Irvine, CA, USA)] (PPVFinger). However, the agreement between PPVFinger and PPV derived from an arterial catheter (PPVART) in obese patients having laparoscopic bariatric surgery is unknown. We compared PPVFinger and PPVART at 6 time points in 60 obese patients having laparoscopic bariatric surgery in a secondary analysis of a prospective method comparison study. We used Bland-Altman analysis to assess absolute agreement between PPVFinger and PPVART. The predictive agreement for fluid responsiveness between PPVFinger and PPVART was evaluated across three PPV categories (PPV < 9%, PPV 9-13%, PPV > 13%) as concordance rate of paired measurements and Cohen's kappa. The overall mean of the differences between PPVFinger and PPVART was 0.5 ± 4.6% (95%-LoA - 8.6 to 9.6%) and the overall predictive agreement was 72.4% with a Cohen's kappa of 0.53. The mean of the differences was - 0.7 ± 3.8% (95%-LoA - 8.1 to 6.7%) without pneumoperitoneum in horizontal position and 1.1 ± 4.8% (95%-LoA - 8.4 to 10.5%) during pneumoperitoneum in reverse-Trendelenburg position. The absolute agreement and predictive agreement between PPVFinger and PPVART are moderate in obese patients having laparoscopic bariatric surgery.

Minute ventilation assessment in the PACU is useful to predict postoperative respiratory depression following discharge to the floor: A prospective cohort study.

STUDY OBJECTIVE: Reliably identifying patients at risk for postoperative respiratory depression (RD) remains an unmet need. We hypothesized that defined low minute ventilation events (LMVe) near the end of the post-anesthesia care unit (PACU) stay identifies patients at RD risk on the general hospital floor (GHF). DESIGN: Prospective observational study. SETTING: Tertiary care, urban academic medical center. PACU and GHF during the first postoperative night. PATIENTS: One hundred-and-nineteen adult, ASA I - III patients undergoing elective surgery under general anesthesia completed the study. INTERVENTIONS: Data collection from a non-invasive respiratory volume monitor and the patients' medical record perioperatively through the first postoperative night. MEASUREMENTS: Minute ventilation (MV), tidal volume (TV) and respiratory rate (RR) were measured continuously in the PACU and on the GHF. MV was counted as the percent of individual predicted MV (MVPRED), and RD was defined as ≥1 LMVe/h on the GHF. Based on the number of LMVes within 30 min before PACU discharge, patients were grouped into A, 'Not-At-Risk': 0 LMVe and B, 'At-Risk': ≥1 LMVes. Unpaired t-test, Mann-Whitney U test, ANOVA, Kruskal-Wallis test, Fisher's exact test, sensitivity and specificity and ROC curve analyses were applied as appropriate. MAIN RESULTS: One hundred-and-six (89%) and 13 (11%) patients met Group A and B criteria respectively. The latter had more LMVe/h on the GHF (median 0.81 vs 0, p ≤ 0.001), and their MVPRED was significantly less. Following opioid administration, the LMVe likelihood was 43% in Group B and 5.6% in Group A. As a predictor for RD on the GHF, the number of LMVe in the last 30 min of PACU, had positive and negative predictive values of 61.5% and 90.6%, respectively. CONCLUSION: Minute ventilation assessment in the PACU as described in this study can be useful to identify patients at risk for postoperative respiratory depression.

Noninfectious Fever in the Near-Term Pregnant Rat Induces Fetal Brain Inflammation: A Model for the Consequences of Epidural-Associated Maternal Fever.

BACKGROUND: Women laboring with epidural analgesia experience fever much more frequently than do women who chose other forms of analgesia, and maternal intrapartum fever is associated with numerous adverse consequences, including brain injury in the fetus. We developed a model of noninfectious inflammatory fever in the near-term pregnant rat to simulate the pathophysiology of epidural-associated fever and hypothesized that it would produce fetal brain inflammation. METHODS: Twenty-four pregnant Sprague-Dawley rats were studied at 20 days gestation (term: 22 days). Dams were treated by injection of rat recombinant interleukin (IL)-6 or vehicle at 90-minute intervals, and temperature was monitored every 30 minutes. Eight hours after the first treatment, dams were delivered of fetuses and then killed. Maternal IL-6 was measured at delivery. Fetal brains (n = 24) were processed and stained for ED-1/CD68, a marker for activated microglia, and cell counts in the lateral septal and hippocampal brain regions were measured. Fetal brains were also stained for cyclooxygenase-2 (COX-2), a downstream marker of neuroinflammation. Eight fetal brains were further analyzed for quantitative forebrain COX-2 by Western blotting compared to a ß-actin standard. Maternal temperature and IL-6 levels were compared between treatments, as were cell counts, COX-2 staining, and COX-2 levels by Mann-Whitney U test, repeated-measures analysis of variance, or Fisher exact test, as appropriate. RESULTS: Injection of rat IL-6 at 90-minute intervals produced an elevation of maternal temperature compared to vehicle (P < .0001). IL-6 levels were elevated to clinically relevant levels at delivery in IL-6 compared to vehicle-treated animals (mean ± standard deviation: 923 ± 97 vs 143 ± 94 pg/mL, P = .0006). ED-1-stained cells were present in significantly higher numbers in fetal brains from IL-6 compared to saline-treated dams (median [interquartile range]: caudal hippocampus, 99 [94-104] and 64 [57-68], respectively, P = .002; lateral septum, 102 [96-111] and 68 [65-69], respectively, P = .002), as well as COX-2 immunostaining (lateral septum, 22 [20-26] and 17 [15-18], respectively, P = .005; dorsal hippocampus, 27 [22-32] and 16 [14-19], respectively, P = .013) and quantitative COX-2 Western blotting activity (mean ± standard error of the mean: vehicle, 0% of ß-actin intensity versus IL-6, 41.5% ± 24%, P < .001). CONCLUSIONS: Noninfectious inflammatory fever is inducible in the near-term pregnant rat by injection of IL-6 at levels comparable to those observed during human epidural labor analgesia. Maternal IL-6 injection causes neuroinflammation in the fetus.

Respiratory volume monitoring in an obese surgical population and the prediction of postoperative respiratory depression by the STOP-bang OSA risk score.

STUDY OBJECTIVE: To evaluate use of a respiratory volume monitor (RVM; ExSpiron, Respiratory Motion, Inc., Waltham, MA, USA) that provides minute ventilation (MV), tidal volume (TV) and respiratory rate (RR) measurements in obese surgical patients, hitherto undescribed. DESIGN: Prospective, IRB-approved observational study of RVM parameter accuracy in obese surgical patients, designed to test the ability of the RVM to detect predefined postoperative respiratory depression (PORD) and apneic events (POA) and to correlate STOP-Bang scores with PORD and POA. SETTING: Pre-, intra-, and post-op patient-care areas, including the post-anesthesia care unit (PACU) in 2 academic centers with bariatric populations. PATIENTS: 80 patients (47±12 years), BMI of 43±7 kg/m(2) undergoing elective surgery were enrolled. INTERVENTIONS: Data collected included patient characteristics, STOP-Bang scores and RVM data from immediately preoperatively through PACU completion without effecting standard clinical care. MEASUREMENTS: Low minute ventilation (LMV) was defined as 40% of predicted MV, and PORD was defined as sustained LMV for 5 minutes. Appropriate parametric and non-parametric statistical analyses were performed, P<.05 considered significant. MAIN RESULTS: In 56 patients with complete intraoperative ventilator data, correlation between RVM and ventilator MV measurements was r=0.89 (measurement bias 1.5%, accuracy 11%). Measurement error was 0.13 L/min (95% confidence interval-0.93 L/min - 1.20 L/min). In PACU, 16.3% and 31% of patients had PORD and POA respectively. There were no significant differences in the incidence of PORD and POA in 3 STOP-Bang risk categories (P>.2). CONCLUSIONS: There was excellent correlation and accuracy between the RVM and ventilator volumes in obese surgical patients. A considerable number of patients exhibited PORD and POA in the PACU. The STOP-Bang risk scores correlated poorly with PORD and POA which suggests that obese surgical patients remain at risk for early post-operative respiratory events irrespective of the STOP-Bang score.

Blood Products, Crystalloids, and Rapid Infusion: An Experimental Study.

BACKGROUND: Electromagnetic coil overheating, deformation, occlusion, and rupture during rapid infuser use have been previously reported. Although the etiology is unclear, prolonged machine use and reconstitution of citrated blood components with crystalloid solutions in the reservoir have been implicated. Lactated Ringer's (LR) solution is of particular concern as a diluent because of its calcium content. We sought to reproduce this failure mode using different infusion rates and different combinations of fluids for blood product reconstitution in the reservoir. We also introduced calcium chloride (CaCl2) to the mix to determine its role in macroscopic clot formation. METHODS: In this in vitro study, we conducted 2 series of experiments using the Belmont FMS 2000 rapid infuser and a reservoir. In series I, we submitted a mix of 1 U fresh thawed plasma (FTP) and 1 U red blood cells (RBC) with 500 mL of LR solution, normal saline, Plasma-Lyte A, or albumin 5% to a specific pump flow sequence. If neither a pump failure mode or self-shutoff (primary outcome) nor macroscopic clot (secondary outcome) was observed during a pump flow sequence, the sequences were repeated after first adding an additional 500 mL of the initially used crystalloid or albumin and then CaCl2 beginning with 200 mg and up to 1 g to the reservoir. In series II, 7 different crystalloid-blood product combinations were tested by using a variety of pump flow sequences with the same end points. Descriptive statistics and analysis of variance were used, and data were reported as means ± SD. RESULTS: We did not observe a Belmont pump failure mode (coil deformation, occlusion, or rupture) as previously described. In series I, the addition of CaCl2 200 mg resulted in macroscopic clots in 9 of 10 experiments (95% confidence interval, 0.55-0.99). The time to clot formation was 9.1 ± 2.3 minutes (99% confidence interval, 6.74-11.46) and did not differ between solutions used for component reconstitution. In series II, adding variable amounts of CaCl2 to 4 different combinations of FTP/RBC with Plasma-Lyte A or LR solution led to clot formation. The use of only FTP in 2 experiments with either LR solution or normal saline resulted in formation of a fibrin clot. In 1 experiment of LR solution mixed with RBCs alone, no clot was observed even after addition of 1 g CaCl2. After the observation of clot in the reservoir, the fluid empty alarm occurred once in series I, the overheating alarm occurred once in series II, and the high-pressure alarms occurred 3 times in each series, all accompanied by self-shutoff. CONCLUSIONS: In this in vitro study, we were unable to reproduce the failure mode characterized by coil overheating, deformation, and rupture previously reported with use of the FMS 2000. Addition of CaCl2 in the range of 200 mg caused macroscopic coagulation in the reservoir when added to crystalloids or albumin mixed with different combinations of blood products containing FTP.

Sodium homeostasis during liver transplantation and correlation with outcomes.

BACKGROUND: Reports of perioperative serum sodium increase in liver transplant (LT) recipients are mostly restricted to unintentional rapid serum sodium overcorrection with subsequent development of central pontine myelinolysis. We examined intraoperative serum sodium changes and their effect on short-term outcomes after LT. METHODS: We retrospectively analyzed data of all LT recipients over a period of 3.5 years. Collected information included preoperative and postoperative serum sodium (Napre and Napost), delta sodium (ΔNa), intraoperative serum sodium peak and trough with corresponding maximum ΔNa, intraoperative peak blood glucose, history of hepatic encephalopathy, perioperative diuretics, intraoperative administration of vasopressin, dopaminergic agents, alkalizing drugs (sodium bicarbonate [NaHCO3], tromethamine), crystalloids, colloids, fresh frozen plasma (FFP), and packed red blood cells (PRBC). The delta of serum osmolality (ΔOsm) was calculated from Napre and Napost, blood urea nitrogen, and blood glucose values, and the correlation between ΔNa and ΔOsm was examined. Outcomes analyzed included intubation for ≥2 days, postanesthesia care unit/surgical intensive care unit (PACU/SICU) length of stay (LOS) for ≥2 days, need of SICU admission, hospital LOS, postoperative neurological complications, and mortality. Univariate and multivariate analyses were performed to test associations between ΔNa and outcomes. A P value <0.005 was considered significant. RESULTS: Data of 164 patients were analyzed. Their ΔNa was 5.3 ± 4.5 (mean ± SD) mEq/L. A lower Napre was associated with greater ΔNa, a relationship likely due to the regression to the mean. In a subgroup of patients with Napre < 130 mEq/L, ΔNa was 11.0 ± 3.6 mEq/L, significantly higher than in normonatremic patients (P < 0.0001). Mortality and neurologic complications were not affected by changes in ΔNa (all P ≥ 0.41). An increase in ΔNa was associated with higher odds of prolonged intubation and prolonged PACU/SICU LOS in univariate and multivariate regression analyses (P = 0.0003 and P = 0.0049, respectively, for adjusted odds ratios). The odds ratios for associations of ΔNa with those outcomes did not differ between patients treated versus not treated with NaHCO3. The intraoperative ΔNa was significantly higher in patients with intraoperative hyperglycemia (P < 0.0001). Intraoperative administration of NaHCO3 and the number of transfused FFP and PRBC units were also associated with a significantly higher ΔNa (P = 0.0001). The ΔNa correlated significantly with ΔOsm. CONCLUSIONS: A larger intraoperative increase in ΔNa is associated with worse recipient short-term outcomes. Patients with preoperative hyponatremia may be at particular risk. ΔNa increases with the intraoperative use of NaHCO3, quantity of FFP, and PRBCs transfused, as well as with intraoperative hyperglycemia. Potential differences on sodium homeostasis between NaHCO3 and tromethamine use for intraoperative pH adjustment should be prospectively investigated.

Phenylephrine as a simulated intravascular epidural test dose in pediatrics: a pilot study.

BACKGROUND: A test dose is used to detect intravascular injection during neuraxial block in pediatrics. Accidental intravascular epidural local anesthetic injection might be unrecognized in anesthetized children leading to potential life-threatening complications. In children, sevoflurane anesthesia blunts the hemodynamic response when intravascular cathecolamines are administered. No studies have explored the hemodynamics and the criteria for a positive test dose result following phenylephrine in sevoflurane anesthetized children. METHODS: Healthy children undergoing minor procedures were randomly assigned to receive intravenous placebo, or 5 µg∙kg(-1) phenylephrine (n = 11/group) during sevoflurane anesthesia. Hemodynamic response was assessed using electrocardiography, pulse oxymetry and non-invasive blood pressure monitoring for 5 min following drug administration in anesthetized patients. RESULTS: All patients receiving phenylephrine showed a decreased heart rate (HR) but not all of them met the positive criterion for test dose response. Overall, at 1 min, patients receiving phenylephrine showed a 25% decrease in HR from the baseline while an increase in blood pressure was noticed in 54% of patients receiving phenylephrine. DISCUSSION: Phenylephrine might be a future indicator of positive intravascular test dose. Further investigation is needed to find out the phenylephrine dose that elicits a reliable hemodynamic response and whether phenylephrine needs to be dose age-adjusted in order to appreciate relevant hemodynamic changes in children receiving neuraxial blocks undergoing general anesthesia.

Performance validation of a modified magnetic resonance imaging-compatible temperature probe in children.

INTRODUCTION: During magnetic resonance imaging (MRI), children are at risk for body temperature variations. The cold MRI environment that preserves the MRI magnet can cause serious hypothermia. On the other hand, hyperthermia may also develop because of radiofrequency-induced heating of the tissues, particularly in prolonged examinations. Because of a lack of MRI-compatible core temperature probes, temperature assessment is unreliable, and specific absorption rate-related patient heat gain must be calculated to determine the allowable scan duration. We compared an MRI-compatible temperature probe and a modification thereof to a standard esophageal core body temperature probe in children. METHODS: Children undergoing general anesthesia were recruited, each patient serving as his/her own control. Core body temperature was measured using 3 different devices: (1) a fiberoptic MRI-compatible skin surface temperature probe (MRI-skin) located on the child's skin surface; (2) a fiberoptic MRI-compatible temperature probe modified with a single-use sleeve at the tip (MRI-core), located in the nasopharynx; and (3) a standard temperature monitor (STRD) located in the esophagus or nasopharynx. The Bland-Altman method was used for statistical analysis. RESULTS: We enrolled 60 children aged 7.8 ± 6 years (mean ± SD) weighing 32.4 (±26.4) kg. The estimated difference between the STRD and MRI-core measurements of core temperature was 0.06°C (confidence interval [CI]: -0.02, 0.15), and between the STRD and the MRI-skin 1.19°C (CI: 0.97, 1.41). According to the Bland-Altman analysis, the 95% limits of agreement ranged from -0.9 to 3.4 and from -1.3 to 1.2 between the STRD and the MRI-skin probe and the MRI-core probe, respectively. DISCUSSION: Our results show good agreement between standard esophageal measurements of core temperature and core temperature measured using a modified MRI-core probe during general anesthesia in a general surgical pediatric population. The ability to accurately assess core temperature in the MRI suite may safely allow longer scan times and therefore reduce repeat anesthetic exposure, improve patient safety, and enhance the quality of care in children.

Intrathecal antinociceptive interaction between the NMDA antagonist ketamine and the opioids, morphine and biphalin.

Biphalin is an opioid peptide analogue that currently is under clinical development as a new type of site-directed analgesic. In rats, the intrathecal (i.t.) analgesic potency of biphalin is 1000-fold greater than morphine. Such a high activity may reflect this compound's activation of three types of opioid receptors (mu, delta and kappa). NMDA receptors also play an important role in nociceptive processing. Therefore, we investigated in rats whether an NMDA antagonist may influence biphalin-induced antinociception. In the present study, ketamine was chosen because of the widespread safe use of this drug in clinical practice. I.t. application of ketamine alone had relatively little analgesic effect and its excitatory effects limited possible doses of the drug. Co-administration of ketamine with biphalin or morphine produced markedly greater antinociception than biphalin or morphine alone in acute, thermal tail flick testing. These results suggest that NMDA antagonists may be useful potentiators of biphalin analgesia. Thus, to obtain the same spinal antinociceptive effect, lower doses of biphalin or morphine are required when ketamine is co-administered.

Extent of right hepatectomy determines postoperative donor albumin and bilirubin changes: new insights.

BACKGROUND: Changes in donor plasma albumin (Alb) and bilirubin (Tbili) are common following right hepatectomy for liver transplantation. We conducted a retrospective study to determine whether the size of the liver resection and the estimated blood loss (EBL) impact these laboratory values in the first week (early) and third week (late) postoperatively. METHODS: Demographics and peri-operative data of 34 donors undergoing right hepatectomy were analysed by Spearman's correlation (data in means+/-SD, P<0.05=statistically significant). Re-admissions for pleural effusions were tracked. RESULTS: Donors were 26-56 (43.3+/-9.1) years old, body mass index (kg/m(2)) was 27.7+/-4.2, liver resected (%) was 58+/-7 and EBL (mL) was 1505+/-927. A larger hepatectomy correlated with lower Alb at 3 weeks (P=0.03) and also with a higher early (P=0.025) and late Tbili (P=0.037). Larger blood loss determined low Alb in the first week (P=0.013), still noticeable 3 weeks postoperatively (P=0.047). Re-admissions for pleural effusion were not associated with the size of the liver resection or postoperative Alb changes. CONCLUSIONS: A remaining liver size-dependent reduced synthetic hepatic function may explain the persistent low Alb that becomes apparent at end of the preoperative Albs half-life. A size-related diminished metabolic liver capacity results in early and late elevated Tbili. Prospective studies are needed to better understand the impact of resection size on hepatic physiology, donor care and clinical outcomes.

Antinociception after intrathecal biphalin application in rats: a reevaluation and novel, rapid method to confirm correct catheter tip position.

The opioid peptide dimmer biphalin [(Tyr-D-Ala-Gly-Phe-NH-)(2)] has high potency both in vivo and in vitro. Its antinociceptive activity depends on the route of administration: the lowest potency is after subcutaneous, and the highest after intrathecal or inracerebroventricular administration. We tested the analgesic activity of biphalin in a wide range of doses after intrathecal administration to rats. Doses as low as 0.005 nmol produced significant analgesia. Increasing the dose up to 2 nmol elevated and prolonged antinociception without any evident side effects, indicating that biphalin is an extremely potent opioid after intrathecal application with a wide therapeutic window. The highest dose tested (20 nmol) produced full analgesia and body rigidity lasting 2-3 h. After muscle tone returned to normal, antinociception lasted for several more hours. During these studies we observed a correlation between responses to biphalin and catheter placement. Postmortem verification of catheter placement revealed that in those rats in which high-dose biphalin did not produce analgesia or muscle rigidity, the catheter was positioned incorrectly or the flow of drug solution was obstructed. Therefore, a secondary conclusion is that assessment of transient rigidity after administration of a high dose of biphalin may be used as an easy method to confirm intrathecal placement of the catheter.

Endomorphins interact with tachykinin receptors.

Soon after the discovery of endomorphins several studies indicated differences between pharmacological effects of endomorphins and other MOR selective ligands, as well as differences between the effects of endomorphin I and endomorphin II. We now propose that these differences are the result of an additional non-opioid property of endomorphins, namely, their weak antagonist properties with respect to tachykinin NK1 and NK1 receptors.

Spinal antinociceptive effects of AA501, a novel chimeric peptide with opioid receptor agonist and tachykinin receptor antagonist moieties.

The use of "multimodal" combination analgesic therapies or novel single molecules possessing multiple analgesic targets is becoming increasingly attractive. In previous experiments we showed that a substance P antagonist injected intrathecally potentiated the antinociceptive effects of potent opioid receptor agonist, biphalin. Based on examination of the biphalin structure-activity relationship, we designed and synthesized a novel chimeric peptide, termed AA501 (N'(Tyr-D-Ala-Gly-Phe), N"(Z-Trp) hydrazide, Z=benzyloxycarbonyl). AA501 consists of an opioid receptor agonist pharmacophore related to biphalin and a substance P receptor antagonist pharmacophore, both linked by a hydrazide bridge. The present study evaluates the ability of a novel chimeric peptide, AA501, to bind to opioid and substance P receptors and to produce antinociception in tail-flick and formalin tests, and in a neuropathic pain model when administered intrathecally to rats.

Altered hematologic profiles following donor right hepatectomy and implications for perioperative analgesic management.

Living liver donors for adult liver transplant recipients undergo extensive liver resection. Partial donor hepatectomies may alter postoperative drug metabolism and hemostasis; thus, the risks and the benefits of pain management for this unique patient population may need to be reassessed. The safety and efficacy of combined epidural analgesia and field infiltration in our initial living liver donor group are presented. A thoracic epidural catheter was placed before general anesthesia in 2 female and 6 male donors (44.2 +/- 11.3 years old, mean +/- standard deviation [SD], range 26-56). At the end of surgery, incisions were infiltrated (bupivacaine 0.25%), and an epidural infusion was used (bupivacaine 0.1% + hydromorphone hydrochloride 0.02%). Clinical outcomes were followed for 5 days. The time sequence of pain intensity on a 0-10 visual analog scale clustered into 3 phases, the intensity of which differed significantly from each other (2.2 +/- 0.6, 0.69 +/- 0.2, and 2.37 +/- 0.3 respectively, P = 0.028). Right shoulder pain was observed in 75% of the donors. Sedation, pruritus, and nausea were minimal. Consistently maximal international normalized ratio elevation occurred at 17.6 +/- 7 hours postoperatively, then slowly declined. Platelet counts were lowest on day 3. No neurologic injury or local anesthetic toxicity was observed. This 2-site approach provided effective, safe, postoperative analgesia for our donors. Universally, coagulopathy ensued, indicating a potentially increased risk for epidural hemorrhage at epidural catheter removal and mandating close postoperative neurologic and laboratory monitoring. Research is needed to advance the understanding of postoperative coagulopathy and hepatic dysfunction in these donors to further optimize their perioperative management, including that of analgesia.

Corticotropin-releasing hormone (CRH) produces analgesia in a thermal injury model independent of its effect on systemic beta-endorphin and corticosterone.

To determine separately the effect of corticotropin-releasing hormone (CRH) on analgesia and on inflammation, rats were assigned to receive CRH 60 microg/kg, CRH 300 microg/kg, morphine 4 mg/kg, or normal saline intravenously 15 min before a burn injury. Two mesh chambers that allowed collection of fluid had been previously implanted subdermally in each rat. The skin overlying the right chamber was subject to thermal injury. The left chamber served as a control. We assessed systemic analgesia, and levels of beta-endorphin and corticosterone in plasma and in chamber fluid before, 1, 4 and 24 h after drug administration. The CRH groups exhibited longer tail flick latencies than the control group (P=0.0001) although the increase in latency was of smaller magnitude than in the morphine group. We did not observe a CRH dose response for analgesia. Plasma corticosterone levels were higher in the CRH 300 microg/kg group than in the normal saline group at 4 h (P=0.03). Levels of beta-endorphin in plasma as well as the levels of corticosterone and beta-endorphin in chambers were similar in the CRH 300 microg/kg group and in the normal saline group (all P values>0.1). Thus, systemically administered CRH produces analgesia in thermal injury independent of its effect on these two markers of local or systemic inflammation.

The effect of short-term epidural local anesthetic blockade on urinary levels of substance P in interstitial cystitis.

UNLABELLED: We investigated the effect of epidural local anesthetic blockade on urinary substance P levels in five patients suffering from painful flare-ups of interstitial cystitis. Urine was collected in 24-h intervals commencing at the onset of an epidural bolus of 0.25% bupivacaine followed by maintenance epidural infusions of 0.05% bupivacaine. Substance P was measured by radioimmunoassay. After initiation of the epidural infusion, urinary substance P levels increased and then declined in all patients. All patients reported a decrease in pain intensity. We hypothesize that acute release, followed by depletion, of substance P from bladder sensory nerve endings accounts for the transient increase of peptide levels in urine and may contribute to the decrease in pain intensity during a 3-day epidural infusion. IMPLICATIONS: Substance P levels in urine initially increased and then declined in a series of 5 patients who achieved pain control by epidural local anesthetic infusion during a flare-up of interstitial cystitis.

Antihyperalgesic effect of simultaneously released hydromorphone and bupivacaine from polymer fibers in the rat chronic constriction injury model.

We aimed to evaluate the antihyperalgesic efficacy of a combination of hydromorphone (HM) and bupivacaine (BP) delivered via controlled release from a biodegradable cylindrical rod. In vivo studies were performed using a rat model of thermal hyperalgesia induced by chronic constriction injury (CCI) of the sciatic nerve with loose ligatures. Poly(lactic-co-glycolic acid) (PLGA) rods (10 mm length, 1 mm diameter) loaded with HM (5 mg per rod), BP (5 mg per rod) or no drug (placebo) were implanted subcutaneously, in single or dual pairs, adjacent to the constriction injury, immediately after nerve ligation. We evaluated the efficacy of two dose levels for each drug, alone or in combination, in attenuating thermal hyperesthesia over a period of 12 days according to a prevention protocol. Plasma levels of drugs released from the rods and also released in an in vitro simulation were evaluated. In vitro studies demonstrated that drug release is maintained for at least 10 days. HM (5 mg) alone and BP (5 mg) alone did not attenuate hyperalgesia. Their combination provided a significant increase in the paw withdrawal latency as compared to single agents or placebo. When the dose in each group was doubled, implanting four rods, significant attenuation of hyperalgesia was observed. Analyses of rods retrieved after termination of experiments (after 12 days) revealed 30% residual HM and 70% residual BP content. Prolonged delivery of HM and BP alone or in combination via locally applied PLGA rods may offer a feasible alternative to provide long-lasting analgesia.