Measurements of pupillary unrest using infrared pupillometry fail to detect changes in pain intensity in patients after surgery: a prospective observational study.

PURPOSE: The pupil displays chaotic oscillations, also referred to as pupillary unrest in ambient light (PUAL). As pain has previously been shown to increase pupillary unrest, the quantitative assessment of PUAL has been considered a possible tool to identify and quantify pain. Nevertheless, PUAL is affected by various states, such as vigilance, cognitive load, or emotional arousal, independent of pain. Furthermore, systematically applied opioids are known to reduce PUAL, thus potentially limiting its usefulness to detect pain or changes in pain intensity. To test the hypothesis that PUAL can reliably identify changes in pain intensity in a clinical setting, we measured PUAL in patients experiencing substantial pain relief when regional anesthesia interventions were applied after surgery. METHODS: We conducted an observational study at an academic surgery centre following institutional review board approval. Eighteen patients with unsatisfactory pain control following surgery underwent regional anesthesia procedures to improve pain control. We used infrared pupillometry to assess pupillary unrest before and after the regional block. We then compared the changes in pupillary unrest with the changes in pain scores (numeric rating scale [NRS], range 0-10). RESULTS: Eighteen patients received epidural anesthesia (n = 14) or peripheral nerve blocks (n = 4), resulting in improvement of mean (standard deviation [SD]) NRS pain scores from 7.2 (1.7) to 1.9 (1.8) (difference in means, -2.2; 95% confidence interval [CI], -6.3 to -4.1; P < 0.001). Nevertheless, pupillary unrest did not change as pain decreased; the mean (SD) PUAL was 0.113 (0.062) before analgesia and 0.112 (0.068) after analgesia (difference in means, -0.001; 95% CI, -0.018 to 0.015; P = 0.88). CONCLUSION: In this prospective observational study, pupillometric measurements of pupillary unrest did not identify changes in pain intensity in a postoperative, predominantly opioid-exposed patient population. While the sample size was small, the use of measurements of pupillary unrest to detect and quantify pain has to be questioned.

RéSUMé: OBJECTIF: La pupille affiche des oscillations chaotiques, également appelées fluctuations du diamètre pupillaire (FDP). Comme il a déjà été démontré que la douleur augmente les troubles pupillaires, l'évaluation quantitative des FDP a été envisagée comme outil potentiel pour identifier et quantifier la douleur. Néanmoins, les FDP sont affectées par divers états, tels que la vigilance, la charge cognitive ou l'excitation émotionnelle, indépendamment de la douleur. De plus, nous savons que l'application systématique d'opioïdes réduit les FDP, ce qui limite potentiellement leur utilité pour détecter la douleur ou les changements d'intensité de la douleur. Pour tester l'hypothèse selon laquelle les FDP permettent d'identifier de manière fiable les changements dans l'intensité de la douleur dans un cadre clinique, nous avons mesuré les FDP chez les patient·es manifestant un soulagement substantiel de la douleur lorsque des interventions d'anesthésie régionale ont été appliquées après la chirurgie. MéTHODE: Nous avons mené une étude observationnelle dans un centre de chirurgie universitaire après avoir obtenu l'approbation du comité d'éthique indépendant. Dix-huit patient·es dont le contrôle de la douleur n'était pas satisfaisant à la suite d'une intervention chirurgicale ont bénéficié d'interventions d'anesthésie régionale pour améliorer le contrôle de la douleur. Nous avons utilisé la pupillométrie infrarouge pour évaluer les fluctuations du diamètre pupillaire avant et après le bloc régional. Nous avons ensuite comparé les changements dans les fluctuations pupillaires avec les changements dans les scores de douleur (échelle d'évaluation numérique [EVA], plage de 0 à 10). RéSULTATS: Dix-huit patient·es ont reçu une anesthésie péridurale (n = 14) ou des blocs nerveux périphériques (n = 4), ce qui a entraîné une amélioration des scores de douleur moyens (écart type [ET]) sur l'EVA de 7,2 (1,7) à 1,9 (1,8) (différence de moyennes, −2,2 ; intervalle de confiance [IC] à 95 %, −6,3 à −4,1; P < 0,001). Néanmoins, les fluctuations du diamètre pupillaire n'ont pas changé à mesure que la douleur diminuait; la moyenne (ET) des FDP était de 0,113 (0,062) avant l'analgésie et de 0,112 (0,068) après l'analgésie (différence de moyennes, −0,001; IC 95 %, −0,018 à 0,015; P = 0,88). CONCLUSION: Dans cette étude observationnelle prospective, les mesures pupillométriques des fluctuations du diamètre pupillaire n'ont pas permis d'identifier de changements dans l'intensité de la douleur dans une population de patient·es postopératoires, principalement exposé·es aux opioïdes. Bien que la taille de l'échantillon soit petite, l'utilisation de mesures des fluctuations du diamètre pupillaire pour détecter et quantifier la douleur doit être remise en question.

Optimizing Uptake of Multimodal Pain Management After Surgery Using the Electronic Health Record.

This quality improvement study evaluates the effect of an electronic health record intervention on multimodal pain management following surgery in 2 randomized clinical trials.

Lidocaine Infusion for the Management of Postoperative Pain and Delirium (LIMPP): protocol for a randomised control trial.

INTRODUCTION: Postoperative delirium is a frequent adverse event following elective non-cardiac surgery. The occurrence of delirium increases the risk of functional impairment, placement to facilities other than home after discharge, cognitive impairment at discharge, as well as in-hospital and possibly long-term mortality. Unfortunately, there is a dearth of effective strategies to minimise the risk from modifiable risk factors, including postoperative pain control and the analgesic regimen. Use of potent opioids, currently the backbone of postoperative pain control, alters cognition and has been associated with an increased risk of postoperative delirium. Literature supports the intraoperative use of lidocaine infusions to decrease postoperative opioid requirements, however, whether the use of postoperative lidocaine infusions is associated with lower opioid requirements and subsequently a reduction in postoperative delirium has not been investigated. METHODS AND ANALYSIS: The Lidocaine Infusion for the Management of Postoperative Pain and Delirium trial is a randomised, double-blinded study of a postoperative 48-hour infusion of lidocaine at 1.33 mg/kg/hour versus placebo in older patients undergoing major reconstructive spinal surgery at the University of California, San Francisco. Our primary outcome is incident delirium measured daily by the Confusion Assessment Method in the first three postoperative days. Secondary outcomes include delirium severity, changes in cognition, pain scores, opioid use, incidence of opioid related side effects and functional benefits including time to discharge and improved recovery from surgery. Lidocaine safety will be assessed with daily screening questionnaires and lidocaine plasma levels. ETHICS AND DISSEMINATION: This study protocol has been approved by the ethics board at the University of California, San Francisco. The results of this study will be published in a peer-review journal and presented at national conferences as poster or oral presentations. Participants wishing to know the results of this study will be contacted directly on data publication. TRIAL REGISTRATION NUMBER: NCT05010148.

Neuraxial and general anesthesia for outpatient total joint arthroplasty result in similarly low rates of major perioperative complications: a multicentered cohort study.

BACKGROUND: Neuraxial anesthesia when compared with general anesthesia has shown to improve outcomes following lower extremity total joint arthroplasty. It is unclear whether these benefits are present in outpatient surgery given the selection of healthier patients. OBJECTIVE: To compare the effects of neuraxial versus general anesthesia on outcomes following ambulatory hip and knee arthroplasty. METHODS: Multicentered retrospective cohort study in ambulatory hip or knee arthroplasty patients between January 2017 and December 2019. Primary endpoint examined 30-day major postoperative complications (mortality, myocardial infarction, deep venous thromboembolism, pulmonary embolism, stroke, and acute renal failure). RESULTS: Of 11 523 eligible patients identified, 10 003 received neuraxial anesthesia, while 1520 received general anesthesia. 30-day major complications did not differ between neuraxial anesthesia and general anesthesia groups (1.8% vs 2.3%; aOR=0.85, CI: 0.56 to 1.27, p=0.39). There was no difference in 30-day minor complications (surgical site infection, pneumonia, urinary tract infection; 3.3% vs 4.1%; aOR=0.83, CI: 0.62 to 1.14, p=0.23). The neuraxial group demonstrated reduced pain and analgesia requirements and had less postoperative nausea and vomiting (PONV). Median recovery room length of stay was shorter by 52 min in the general anesthesia group, but these patients were more likely to fail same day discharge (33% vs 23.4%; p<0.01). CONCLUSION: Anesthesia type was not associated with an increased risk for complications. However, neuraxial anesthesia improved outcomes that predict readiness for discharge: patients had less pain, required less opioids, and had a lower incidence of PONV, thus improving the rate of same day discharge. TRIAL REGISTRATION NUMBER: NCT04203732.

Perioperative outcomes for patients on chronic buprenorphine undergoing spine surgery: A case series.

OBJECTIVE: Pain management following spine surgery can be challenging as patients routinely suffer from chronic pain and opioid tolerance. The increasing popularity of buprenorphine use for pain management in this population may further complicate perioperative pain management due to the limited efficacy of other opioids in the presence of buprenorphine. This study describes perioperative management and outcomes in patients on chronic buprenorphine who underwent elective inpatient spine surgery. DESIGN: The authors performed a retrospective chart review of all patients >18 years of age taking chronic buprenorphine for any indication who had elective inpatient spine surgery at a single institution. Perioperative pain management data were analyzed for all patients who underwent spine surgery and were maintained on buprenorphine during their hospital stay. SETTING: The study was performed at a single tertiary academic medical center. MAIN OUTCOME MEASURES: The primary outcome measures were post-operative pain scores and analgesic medication requirements. RESULTS: Twelve patients on buprenorphine underwent inpatient spine surgery. Acceptable pain control was achieved in all cases. Management included preoperative dose limitation of buprenorphine when indicated and the extensive use of multimodal analgesia. CONCLUSION: The question whether patients presenting for painful, elective surgery should continue using buprenorphine perioperatively is an area of controversy, and the present manuscript provides more evidence for the concept of therapy continuation with buprenorphine.

Extraplexus versus intraplexus ultrasound-guided interscalene brachial plexus block for ambulatory arthroscopic shoulder surgery: A randomized controlled trial.

BACKGROUND: This randomized study compared the efficacy and safety of extraplexus and intraplexus injection of local anesthetic for interscalene brachial plexus block. METHODS: 208 ASA I-II patients scheduled for elective shoulder arthroscopy under general anesthesia and ultrasound-guided interscalene brachial plexus block were randomly allocated to receive an injection of 25mL ropivacaine 0.5% either between C5-C6 nerve roots (intraplexus), or anterior and posterior to the brachial plexus into the plane between the perineural sheath and scalene muscles (extraplexus). The primary outcome was time to loss of shoulder abduction. Secondary outcomes included block duration, perioperative opioid consumption, pain scores, block performance time, number of needle passes, onset of sensory blockade, paresthesia, recovery room length of stay, patient satisfaction, incidence of Horner's syndrome, dyspnea, hoarseness, and post-operative nausea and vomiting. RESULTS: Time to loss of shoulder abduction was faster in the intraplexus group (log-rank p-value<0.0005; median [interquartile range]: 4 min [2-6] vs. 6 min [4-10]; p-value <0.0005). Although the intraplexus group required fewer needle passes (2 vs. 3, p<0.0005), it resulted in more transient paresthesia (35.9% vs. 14.5%, p = 0.0004) with no difference in any other secondary outcome. CONCLUSION: The intraplexus approach to the interscalene brachial plexus block results in a faster onset of motor block, as well as sensory block. Both intraplexus and extraplexus approaches to interscalene brachial plexus block provide effective analgesia. Given the increased incidence of paresthesia with an intraplexus approach, an extraplexus approach to interscalene brachial plexus block is likely a more appropriate choice.

Editorial Commentary: Neuraxial Anesthesia Improves Pain After Hip Arthroscopy but Risks Ambulatory Discharge Delay.

Hip arthroscopy continues to be one of the fastest-growing orthopaedic procedures nationally, and pain control following these procedures can be challenging. As regional anesthesia techniques for this population have shown to have limited benefits, pain management for hip arthroscopy focused on multimodal analgesia and preventive analgesia, interventions that reduce postoperative hyperalgesia. The use of neuraxial anesthesia such as spinal and epidural anesthesia, established preventive analgesic anesthetic techniques, has demonstrated to improve postoperative pain in orthopaedic surgery when compared with general anesthesia. This promising finding highlights that despite potential disadvantages of neuraxial anesthesia, such as a small risk for complications or delayed resolution of the neuraxial block that could delay discharge, neuraxial anesthesia could be a suitable anesthetic technique for ambulatory orthopaedic surgery.

Comparison of programmed intermittent epidural bolus and continuous epidural infusion for post-operative analgesia after major abdominal surgery: A randomized controlled trial.

STUDY OBJECTIVE: Few studies have compared continuous epidural infusion (CEI) against programmed intermittent epidural bolus (PIEB) epidural analgesia after major abdominal surgery. It has not been established whether the modality of epidural medication administration affects postoperative pain and other patient outcomes. The goal of this study was to compare the efficacy of PIEB against CEI in postoperative pain management after a broad range of surgeries with abdominal incisions, all managed in the context of an established enhanced recovery after surgery (ERAS) pathway. DESIGN: Prospective, randomized, controlled trial. SETTING: Postoperative acute care. PATIENTS: 120 patients scheduled for major surgery involving abdominal incisions with planned postoperative epidural analgesia were enrolled as study participants. INTERVENTIONS: All subjects received a standardized epidural solution containing ropivacaine 0.0625% and fentanyl 2 µg/ml. The CEI group received this solution as a continuous infusion, while the PIEB group received this solution as programmed intermittent boluses. MEASUREMENTS: The primary study outcome was the total local anesthetic used over the first 24 h post-operatively. Secondary outcomes included pain severity, pain interference, total opioid consumption, patient satisfaction, and adverse effects at 24, 48, and 72 h postoperatively. MAIN RESULTS: There was no difference in the primary outcome of total amount of local anesthetic administered in the first 24-hour postoperative period (PIEB: 123 mg [Interquartile Range (IQR): 114-136]; CEI: 126 mg [IQR: 120-134]). There were also no differences in average pain severity, total opioid consumption, patient satisfaction, number of PCEA requests and incidence of adverse events at 24, 48, and 72 h postoperatively. CONCLUSIONS: Our study suggests that within the context of an established ERAS program, PIEB and CEI modes of epidural analgesia can be equally efficacious and safe in providing postoperative analgesia after major abdominal surgery.

Suppression of pupillary unrest by general anesthesia and propofol sedation.

The pupil undergoes irregular oscillations when exposed to light. These oscillations, known as pupillary unrest in ambient light, originate from oscillatory activity within the Edinger-Westphal nucleus in the midbrain. The midbrain and upper pons also contain nuclei known to be very sensitive to the effects of anesthetics that play a central role in maintaining wakefulness. We hypothesized that anesthetics may display similar effects on wakefulness and pupillary unrest. Repeat measurements of pupillary unrest using infrared pupillometry were performed in 16 patients undergoing general anesthesia and 8 patients undergoing propofol sedation. Pupil scans were analyzed using fast Fourier transformation to quantify the effects of the anesthetics on pupillary unrest. During general anesthesia and deep sedation, observed pupillary unrest values below 0.1 (AU) indicate complete suppression of pupillary oscillations. Pupillary unrest decreased more during general anesthesia [to 24% of baseline (95% CI 17-30%)] than pupil size [51% of baseline (95% CI 45-57%)]. Sedation with propofol was associated with a reduction in pupillary unrest that was correlated to the depth of sedation as assessed by the Richmond Agitation-Sedation Scale and the processed electroencephalogram. Pupillary unrest is caused by oscillatory activity within the midbrain that is affected by the state of wakefulness or by hypnotics directly. Increased sedation and general anesthesia reduce and then abolish pupillary unrest as wakefulness decreases. We speculate that midbrain nuclei responsible for wakefulness and pupillary unrest are either communicating or share a similar sensitivity to the effects of commonly used anesthetics.

Preoperative Fascia Iliaca Block Does Not Improve Analgesia after Arthroscopic Hip Surgery, but Causes Quadriceps Muscles Weakness: A Randomized, Double-blind Trial.

WHAT WE ALREADY KNOW ABOUT THIS TOPIC: WHAT THIS ARTICLE TELLS US THAT IS NEW: BACKGROUND:: Ambulatory hip arthroscopy is associated with postoperative pain routinely requiring opioid analgesia. The potential role of peripheral nerve blocks for pain control after hip arthroscopy is controversial. This trial investigated whether a preoperative fascia iliaca block improves postoperative analgesia. METHODS: In a prospective, double-blinded trial, 80 patients scheduled for hip arthroscopy were randomized to receive a preoperative fascia iliaca block with 40 ml ropivacaine 0.2% or saline. Patients also received an intraarticular injection of 10-ml ropivacaine 0.2% at procedure end. Primary study endpoint was highest pain score reported in the recovery room; other study endpoints were pain scores and opioid use 24 h after surgery. Additionally, quadriceps strength was measured to identify leg weakness. RESULTS: The analysis included 78 patients. Highest pain scores in the recovery room were similar in the block group (6 ± 2) versus placebo group (7 ± 2), difference: -0.2 (95% CI, -1.1 to 0.7), as was opioid use (intravenous morphine equivalent dose: 15 ± 7mg [block] vs. 16 ± 9 mg [placebo]). Once discharged home, patients experienced similar pain and opioid use (13 ± 7 mg [block] vs. 12 ± 8 mg [placebo]) in the 24 h after surgery. The fascia iliaca block resulted in noticeable quadriceps weakness. There were four postoperative falls in the block group versus one fall in the placebo group. CONCLUSIONS: Preoperative fascia iliaca blockade in addition to intraarticular local anesthetic injection did not improve pain control after hip arthroscopy but did result in quadriceps weakness, which may contribute to an increased fall risk. Routine use of this block cannot be recommended in this patient population.

Prediction of Opioid Analgesic Efficacy by Measurement of Pupillary Unrest.

BACKGROUND: Pupillary unrest under ambient light (PUAL) is the fluctuation in pupil diameter in time around a mean value. PUAL is augmented by light and diminished by administration of opioids. We hypothesized that, because pupillary unrest is a marker of opioid effect, low levels of PUAL may be associated with reduced opioid efficacy, as measured by changes in the numerical rating scale (NRS) pain scores of patients in the postanesthesia care unit (PACU). METHODS: We used an infrared pupillometer to measure PUAL in patients recovering from ambulatory surgery at 2 different institutions. At both sites, PUAL was quantified using spectral analysis of the Fourier transform of pupil diameter versus time. We measured PUAL and pain scores before and after opioid administration. Protocols for total capture time and lighting conditions varied between the 2 sites. Correlations between PUAL and change in NRS scores were examined using significance testing of Pearson correlation coefficients. Correlations between change in PUAL and change in NRS scores were also examined. Patients were divided into high and low PUAL groups, and high and low response to opioid. A Fisher exact test was used to determine whether there was a significant association between PUAL and opioid response. RESULTS: For patients with pain in the PACU, low levels of pupillary unrest before opioid therapy were associated with minimal or no reduction in pain scores after opioid administration. We noted a significant correlation at both sites between PUAL and pain score reduction with opioids (r = 0.59, P = .0053, and r = 0.57, P = .022.) The Fisher exact test confirmed that patients with PUAL levels above the mean had a more beneficial analgesic effect from opioids than those with low PUAL levels (P = .018). We also noted that change in PUAL was significantly correlated with change in pain score at both sites (r = 0.56, P = .03 and r = 0.55, P = .01). CONCLUSIONS: We observe that the pretreatment magnitude of PUAL is correlated with the analgesic response to opioid therapy, and that patients who exhibit higher levels of PUAL change after opioid administration have a more beneficial analgesic effect from opioids. Larger studies with uniform measurement protocols are required to confirm these preliminary results.

Combined preoperative femoral and sciatic nerve blockade improves analgesia after anterior cruciate ligament reconstruction: a randomized controlled clinical trial.

STUDY OBJECTIVE: To compare preoperative femoral (FNB) with combined femoral and sciatic nerve block (CFSNB) in patients undergoing arthroscopic anterior cruciate ligament (ACL) reconstruction. DESIGN: Prospective, randomized clinical trial. SETTING: Ambulatory surgery center affiliated with an academic medical center. PATIENTS: Sixty-eight American Society of Anesthesiology physical status I and II patients undergoing arthroscopic ACL reconstruction. INTERVENTIONS: Subjects randomized to the CFSNB group received combined femoral and sciatic nerve blocks preoperatively, whereas patients randomized to the FNB group only received femoral nerve block preoperatively. Both groups then received a standardized general anesthetic with a propofol induction followed by sevoflurane or desflurane maintenance. Intraoperative pain was treated with fentanyl. Pain in the postanesthesia care unit (PACU) was treated with ketorolac and opiates. Patients with significant pain despite ketorolac and opiates could receive a rescue nerve block. MEASUREMENTS: Our primary outcome variable was highest Numeric Rating Scale (NRS) pain score in PACU. NRS pain scores, opioid consumption, opioid adverse effects, and patient satisfaction were assessed perioperatively until postoperative day 3. MAIN RESULTS: The highest PACU NRS pain score was significantly higher in the FNB group compared with the CFSNB group (7 [3-10] vs 5 [0-10], P=.002). The FNB group required significantly larger doses of opioids perioperatively (31.8 vs 19.8mg intravenous morphine equivalents, P<.001). PACU length of stay was significantly longer in the FNB group (128.2 vs 103.1minutes, P=.006). There was no significant difference in opioid consumption, pain scores, or patient satisfaction on postoperative days 1-3 between groups. CONCLUSIONS: Preoperative CFSNB for arthroscopic ACL reconstruction improves analgesia, decreases opioid consumption perioperatively, and decreases PACU length of stay when compared with FNB alone.

Fentanyl, an agonist at the mu opioid receptor, depresses pupillary unrest.

Pupillary unrest is a chaotic fluctuation in pupil size that is observed in darkness with the onset of drowsiness, and in ambient light. The mechanism of pupillary unrest in darkness as well as in ambient light is unknown but studies suggest that it is caused by fluctuating activity in the Edinger-Westphal (E.W.) nucleus. Neurons in the periaqueductal gray with oscillating firing patterns that are inhibitory to the E.W. nucleus have been described in the cat. We theorized that such oscillating neurons produce pupillary unrest in light and would be depressed by agents, such as opioids, known to depress inhibitory pathways in the midbrain. An infrared pupillometer was used to measure the effect of light on pupillary unrest in eight volunteer subjects, and on 20 patients scheduled for knee arthroscopy who received fentanyl as premedication. Pupillary unrest was quantified through spectral analysis of fast Fourier transforms. Sixteen-second measurements of pupil size at 33 Hz were filtered to eliminate blink artifacts and baseline drift. Pupillary unrest was augmented by excitation of the E.W. nucleus by light and was depressed by 40 ± 20% after the administration of the moderate dose of 1 mcg/kg of fentanyl. Recovery from the drug effect was observed. Based upon the data from this study we propose that pupillary unrest in light originates within oscillating inhibitory neurons that intermittently depress the E. W. nucleus.

Association between intraoperative blood transfusions and early postoperative delirium in older adults.

OBJECTIVES: To determine whether intraoperative blood transfusion, a known trigger and amplifier of inflammation, is an independent risk factor for early postoperative delirium (POD), an acute state of confusion with fluctuating consciousness and inattention after surgery, in older adults undergoing surgery. DESIGN: Secondary analysis using a database created for a prospective cognitive outcomes study. SETTING: University hospital. PARTICIPANTS: Four hundred seventy-two individuals aged 65 and older undergoing major noncardiac surgery. MEASUREMENTS: Perioperative data were examined for association with POD on the first postoperative day. Multivariable logistic regression analysis was conducted to determine whether intraoperative blood transfusion independently predicts POD after adjusting for covariates known to be associated with onset of delirium and blood transfusions. RESULTS: One hundred thirty-seven individuals (29%) developed delirium on the first postoperative day. The multivariable logistic regression model identified age, sex, history of central nervous system disorder, preoperative cognitive dysfunction, and pain, as well as blood transfusions, as independent risk factors for POD. Intraoperative administration of more than 1,000 mL of red blood cells (RBCs) was the strongest predictor of POD on the first postoperative day (odds ratio = 3.68; 95% confidence interval = 1.32­10.94; P < .001). CONCLUSION: Intraoperative blood transfusion of more than 1,000 mL of RBCs increases the risk of delirium on the first postoperative day in older adults undergoing noncardiac surgery.

Short passive cooling protects rats during hepatectomy by inducing heat shock proteins and limiting the induction of pro-inflammatory cytokines.

BACKGROUND: Prolonged hepatic warm ischemia during surgery remains a significant problem, particularly in the setting of liver resection and reduced remaining liver mass. The goal of the present study is to evaluate the effect of passive cooling caused by exposure to ambient conditions on hepatic injury in rats during warm ischemia followed by hepatectomy. METHODS: The left and median lobes of male rats were exposed to 75 min of ischemia under either normothermic (37 degrees C) or mildly hypothermic (34 degrees C) conditions. After 75 min of ischemia, the right lobe was resected, leaving the animal with only the remaining ischemic lobes. Animals were allowed to survive indefinitely or sacrificed at 4 h after reperfusion for determination of injury and inflammatory gene expression. RESULTS: Survival was already markedly higher in mildly hypothermic rats than normothermic rats at 24 h. Short passive cooling for the time course of the ischemic event significantly increased the hepatic induction of heat shock proteins 70 and 32 (both 3-fold versus normothermia, P<0.05) in response to ischemia/reperfusion whereas it significantly decreased the induction of tumor necrosis factor-alpha (TNF-alpha) and macrophage inflammatory protein-2 (MIP-2) in the liver. Biochemical markers of hepatic injury were significantly lower in the passive cooling group than in normothermic animals: aspartate aminotransferase (AST) serum concentrations were 9277+/-3461IU/L versus 15106+/-4104IU/L (P<0.01), and alanine aminotransferase (ALT) levels 5986+/-2246IU/L versus 9429+/-3643IU/L (P<0.01). CONCLUSION: We demonstrated in a clinically relevant model of hepatic ischemia/reperfusion that mild hypothermia significantly reduces hepatic injury and improves survival.

Acute hyperglycemia worsens hepatic ischemia/reperfusion injury in rats.

BACKGROUND/AIMS: Acute hyperglycemia is known to worsen ischemia/reperfusion (I/R) injury following myocardial infarction and stroke. We investigated whether acute hyperglycemia worsens injury and amplifies the inflammatory response evoked by hepatic I/R. METHODS: Rats were pretreated with an intraperitoneal injection of 25% glucose or 0.9% sodium chloride (10 ml/kg BW). Subsequently, rats underwent partial (70%) hepatic ischemia for 45 min. After 4 h of reperfusion, hepatic injury, oxidative stress, inflammation, and heat shock protein expression were assessed. RESULTS: Liver injury was increased in the hyperglycemic group with alanine aminotransferase (ALT) and aspartate aminotransferease (AST) serum concentrations of 7,832 +/- 3,374 and 10,677 +/- 4,110 U/L compared to 3,245 +/- 2,009 and 5,386 +/- 3,393 U/L (p < 0.05 vs. control). Hyperglycemic I/R was associated with increased liver nitrotyrosine concentrations and increased neutrophil infiltration. I/R upregulated the protective heat shock proteins HSP32 and HSP70 in control animals, but this protective mechanism was inhibited by hyperglycemia: HSP32 expression decreased from 1.97 +/- 0.89 (control) to 0.46 +/- 0.13 (hyperglycemia), HSP70 expression decreased from 18.99 +/- 11.55 (control) to 3.22 +/- 0.56 (hyperglycemia), (expression normalized to sham, both p < 0.05 vs. control I/R). CONCLUSIONS: Acute hyperglycemia worsens hepatic I/R injury by amplifying oxidative stress and the inflammatory response to I/R. The increase in injury is associated with a downregulation of the protective heat shock proteins HSP32 and HSP70.

Transient hyperglycemia affects the extent of ischemia-reperfusion-induced renal injury in rats.

BACKGROUND: Chronic hyperglycemia is known to increase renal injury, particularly during ischemia-reperfusion episodes. The goal of this study was to examine whether transient hyperglycemia during or after renal ischemia-reperfusion increased renal dysfunction. METHODS: Male Lewis rats underwent sham operations or unilateral nephrectomies followed by contralateral renal ischemia-reperfusion. Hyperglycemic rats were given 25% dextrose to induce transient hyperglycemia lasting throughout the duration of ischemia (PI rats) or beginning 2 h after initiation of reperfusion (PR rats). Additional vehicle control rats received saline and underwent ischemia-reperfusion surgery as with PI and PR rats. Twenty-five minutes of mild renal ischemia followed by 24 h of reperfusion was induced by occluding the renal artery and vein. RESULTS: Terminal serum creatinine concentrations were significantly higher in the PI rats when compared with the PR or vehicle control rats. Histology demonstrated significantly increased necrosis in the PI rats relative to PR and control animals. Tissue analyses demonstrated significantly higher heat shock protein 70, heat shock protein 32, and cleaved caspase-3 protein levels in the PI rats. Oxidative stress generated through the xanthine pathway in the PI group was significantly increased compared with the oxidative stress in the PR and vehicle control rats. In contrast, vascular endothelial growth factor and erythropoietin were significantly decreased in the PI rats compared with the PR rats and controls. CONCLUSIONS: Hyperglycemia that occurred during renal ischemia-reperfusion resulted in severe functional injury compared with normoglycemia or with hyperglycemia that occurred after reperfusion. Investigated molecular pathways are more profoundly affected by hyperglycemia that occurs before renal ischemia-reperfusion.

Increased severity of renal ischemia-reperfusion injury with venous clamping compared to arterial clamping in a rat model.

BACKGROUND: Arterial inflow occlusion is a well-known mechanism of renal injury during major vascular surgery. In contrast, renal injury from venous outflow obstruction is poorly understood. The goal of this study was to examine the injury pattern of renal venous outflow obstruction, compare this with the traditional model of arterial occlusion, and examine possible mechanisms. METHODS: Male Fisher rats were used for the renal warm ischemia model. Twenty-five minutes of renal ischemia was induced by selectively occluding either the renal artery or vein. After 24 h of reperfusion, whole blood and kidney tissue were collected for further analysis. RESULTS: Serum creatinine (SCr) concentrations taken 24 h after reperfusion were significantly greater in the venous occlusion group (V) when compared to the arterial group (A). While histology did not demonstrate significant differences in extent of necrosis between both groups, a stronger inflammatory response resulted from venous occlusion. Specifically, significantly greater MCP-1 mRNA and significantly greater MCP-1, TNF-alpha, and HO-1 protein levels were found in the venous group, while no differences in MIP-2, ICAM-1, and VCAM-1 mRNA expression existed between A and V. Further analysis demonstrated presence of increased cleaved caspase-3 protein in the artery group than in the venous group. CONCLUSIONS: Venous renal outflow obstruction results in more severe functional renal injury when compared to arterial inflow occlusion. Macrophage activation and neutrophilic infiltration appear to be exaggerated during venous occlusion.

Remote renal injury following partial hepatic ischemia/reperfusion injury in rats.

Liver ischemia/reperfusion has been shown to result in injury of remote organs such as the heart and lungs. Whether or not acute liver injury also results in kidney injury has so far not been adequately addressed. In anesthetized Wistar rats, partial (70%) normothermic hepatic ischemia was applied for 75 min. After 24 h of reperfusion, renal injury was assessed by histology, creatinine and blood urea nitrogen (BUN) serum concentrations, renal expression of proinflammatory genes [quantitative real-time polymerase chain reaction (qRT-PCR)], caspase-3 activation (Western blot), and neutrophil accumulation (myeloperoxidase assay). Twenty-four hours after hepatic ischemia, creatinine (0.57+/-0.06 vs. 0.32+/-0.04 mg/dL) and BUN (40.7+/-15.3 vs. 14.3+/-2.0 mg/dL) were increased when compared to sham. qRT-PCR revealed higher renal intercellular adhesion molecule-1 gene expression following hepatic ischemia (166+/-45% when compared to sham) but no differences in renal monocyte chemoattractant protein-1, macrophage inflammatory protein-2, and inducible NO synthase expression. In both groups, kidneys showed no morphological damage and no increase in caspase-3 and myeloperoxidase activity. Severe hepatic ischemia results in a moderate impairment of renal function in rats but does not trigger an inflammatory response in the kidney and does not result in morphological damage of the kidney.

Central venous pressure monitoring during living right donor hepatectomy.

Low central venous pressure (CVP) has been advocated during liver resection to reduce blood loss and transfusion requirements. As a consequence, CVP catheter placement has been considered essential for hepatic surgery, including living donor hepatectomies. We retrospectively analyzed whether intraoperative management without CVP monitoring influenced fluid administration, blood loss, and patient outcome. Medical charts and hospital data system of 50 adult to adult living liver donors were retrospectively reviewed. Data collection included patient demographics, intraoperative variables such as fluid management, blood loss, urine output, and operating room time. Postoperative variables were collected during the postanesthesia care unit stay and for the first 24 hours after surgery. Patients were then grouped on the basis of the presence or absence of a CVP catheter. Data were reanalyzed and groups compared. Patient groups did not differ in terms of demographics at baseline. When divided into groups with CVP and without CVP, the presence of CVP did not result in decreased intraoperative fluid administration. All patients were hemodynamically stable, and renal function was not different between groups throughout hospitalization. Length of postanesthesia care unit and hospital stay was the same. There was no difference in the frequency of complications during the hospital stay and at 3 months' follow-up. CVP monitoring did not appear to reduce blood loss when compared with patients without CVP monitoring. In centers with extensive experience, CVP monitoring may not be necessary in this highly selective patient population.