Randomized controlled trial of 7, 28, vs 42 day stored red blood cell transfusion on oxygen delivery (VO2 max) and exercise duration.

BACKGROUND: Few studies have rigorously assessed the impact of red blood cell (RBC) transfusion on oxygen delivery. Several large trials demonstrated no clinical outcome differences between transfusion of shorter-storage vs prolonged-storage RBCs. These trials did not directly assess functional measures of oxygen delivery. Therefore, it is not clear if 42-day stored RBCs deliver oxygen as effectively as 7-day stored RBCs. STUDY DESIGN AND METHODS: Leukocyte-reduced RBCs were collected by apheresis in AS-3. Thirty subjects were randomized (1:1:1) to receive 2 units of autologous RBCs at either 7, 28, or 42 days following donation. VO2 max testing, using a standardized protocol to exhaustion, was performed 2 days before (Monday) and 2 days after (Friday) the transfusion visit (Wednesday). The primary endpoint was the percent increase in VO2 max between Monday and Friday. The secondary endpoint was the percent change in duration of exercise for the same time points. RESULTS: Hemoglobin levels decreased by 2.8 ± 1.4 g/dL after donation and increased by 2.1 ± 0.6 g/dL after transfusion. This change in hemoglobin was associated with expected decreases (then increases after transfusion) in VO2 max and exercise duration. No differences were observed between 7-day and 42-day RBC transfusion for percent increase in median [IQR] VO2 max (10.5 [0.2-17.3] vs 10.9 [5.7-16.8], P = .41) or for percent increase in exercise duration (5.4 [4.1-6.9] vs 4.9 [2.0-7.2], P = .91), respectively. Results were similar for 28-day RBCs and were consistent across the ITT and per-protocol analysis populations. CONCLUSION: These data indicate that 42-day, 28-day, and 7-day RBCs have similar ability to deliver oxygen.

A randomized-controlled trial of sugammadex versus neostigmine: impact on early postoperative strength.

BACKGROUND: Residual neuromuscular blockade after surgery is associated with airway obstruction, hypoxia, and respiratory complications. Compared with neostigmine, sugammadex reverses neuromuscular blockade to a train-of-four ratio > 0.9 more rapidly. It is unknown, however, whether the superior reversal profile of sugammadex improves clinically relevant measures of strength in the early postoperative period. METHODS: Patients undergoing general, gynecological, or urologic surgery were randomized to receive either neostigmine (70 µg·kg-1, maximum 5 mg) or sugammadex (2 or 4 mg·kg-1) to reverse neuromuscular blockade. The primary outcome was the ability to breathe deeply measured by incentive spirometry at 30, 60, and 120 min after reversal. RESULTS: We randomized 62 patients to either a neostigmine (n = 31) or sugammadex (n = 31) group. The incentive spirometry volume recovery trajectory was not different between the two groups (P = 0.35). Median spirometry volumes at baseline, 30, 60, and 120 min postoperatively were 2650 vs 2500 mL, 1775 vs 1750 mL, 1375 vs 2000 mL, and 1800 vs 1950 mL for the sugammadex and neostigmine groups, respectively. Postoperative incentive spirometry decrease from baseline was not different between the two groups. Hand grip strength, the ability to sit unaided, train-of-four ratio on postanesthesia care unit (PACU) admission, time to extubation, time to PACU discharge readiness, and Quality of Recovery-15 scores were also not different between the groups. CONCLUSIONS: Measures of postoperative strength, such as incentive spirometry, hand group strength, and the ability to sit up in the early postoperative period were not different in patients who received neostigmine or sugammadex for the reversal of neuromuscular blockade. TRIAL REGISTRATION: www.clinicaltrials.gov (NCT02909439); registered: 21 September, 2016.

RéSUMé: CONTEXTE: Les blocs neuromusculaires résiduels après une chirurgie sont associés à l'obstruction des voies aériennes, à l'hypoxie et à des complications respiratoires. Par rapport à la néostigmine, le sugammadex neutralise le bloc neuromusculaire à un ratio de train-de-quatre (TOF) > 0,9 plus rapidement. Nous ne savons toutefois pas si le profil de neutralisation supérieur du sugammadex améliore les mesures pertinentes d'un point de vue clinique de la force en période postopératoire initiale. MéTHODE: Nous avons randomisé des patients subissant une chirurgie générale, gynécologique ou urologique à recevoir de la néostigmine (70 µg·kg-1, maximum 5 mg) ou du sugammadex (2 ou 4 mg·kg-1) pour neutraliser le bloc neuromusculaire. Le critère d'évaluation principal était la capacité des patients à respirer profondément telle que mesurée par spirométrie incitative à 30, 60 et 120 min après la neutralisation. RéSULTATS: Au total, 62 patients ont été randomisés dans les groupes néostigmine (n = 31) ou sugammadex (n = 31). Aucune différence dans la trajectoire de récupération de volume de spirométrie incitative n'a été observée entre les deux groupes (P = 0,35). Les volumes médians de spirométrie préopératoire et à 30, 60 et 120 min postopératoires étaient de 2650 vs 2500 mL, 1775 vs 1750 mL, 1375 vs 2000 mL, et 1800 vs 1950 mL pour les groupes sugammadex et néostigmine, respectivement. La diminution postopératoire de la spirométrie incitative par rapport aux valeurs de base était similaire dans les deux groupes. La force de préhension, la capacité à s'asseoir sans assistance, le ratio de train-de-quatre à l'admission à la salle de réveil, le délai jusqu'à l'extubation, le délai jusqu'à l'obtention des critères de congé de la salle de réveil et les scores de QoR-15 (mesurant la qualité de récupération) ne différaient pas non plus entre les groupes. CONCLUSION: Les mesures de la force postopératoire, telles que la spirométrie incitative, la force de préhension et la capacité de s'asseoir en période postopératoire initiale, ne différaient pas entre les patients ayant reçu de la néostigmine ou du sugammadex pour neutraliser le bloc neuromusculaire. ENREGISTREMENT DE L'éTUDE: www.clinicaltrials.gov (NCT02909439); enregistrée le 21 septembre 2016.

Intrathecal morphine administration reduces postoperative pain and peripheral endocannabinoid levels in total knee arthroplasty patients: a randomized clinical trial.

BACKGROUND: The primary goal of this study was to determine whether administration of intrathecal morphine reduces postoperative pain. The secondary goal was to determine the effect of intrathecal morphine upon circulating levels of the weakly analgesic endocannabinoids, anandamide (AEA) and 2-arachidonoylglycerol (2-AG), and the related lipids palmitoylethanolamide (PEA) and oleoylethanolamide (OEA). METHODS: Forty two total knee arthroplasty (TKA) patients were enrolled in a prospective, double-blinded, randomized study. The intervention consisted of intrathecal morphine (200 µg) or placebo administered at the time of the spinal anesthesia. Postoperative pain was measured during the first 4 h after surgery while serum levels of AEA, 2-AG, PEA, OEA, and cortisol were measured at baseline and 4 h after surgery. RESULTS: Administration of intrathecal morphine reduced postoperative pain 4 h after TKA surgery compared to placebo (p = 0.005) and reduced postoperative systemic opioid consumption (p = 0.001). At baseline, intrathecal morphine led to a significant reduction in AEA, 2-AG, and OEA levels but did not affect PEA or cortisol levels. In patients administered intrathecal placebo, 2-AG levels were elevated 4 h after surgery; whereas patients receiving intrathecal morphine showed reductions in AEA, PEA, and OEA when compared to placebo. At 4 h after TKA surgery cortisol levels were significantly elevated in the placebo group and reduced in those receiving morphine. CONCLUSIONS: These results indicate that intrathecal morphine reduces postoperative pain in TKA patients. Furthermore, activation of central opioid receptors negatively modulates the endocannabinoid tone, suggesting that potent analgesics may reduce the stimulus for production of peripheral endocannabinoids. This study is the first to document the existence of rapid communication between the central opioid and peripheral endocannabinoid systems in humans. TRIAL REGISTRATION: This trial was registered retrospectively. TRIAL REGISTRY: NCT02620631 . Study to Examine Pain Relief With Supplemental Intrathecal Morphine in TKA Patients, NCT02620631 , 12/03/2015.

Interleukin-6 and leptin levels are associated with preoperative pain severity in patients with osteoarthritis but not with acute pain after total knee arthroplasty.

BACKGROUND: Identifying drivers of pain that can serve as novel drug targets is important for improving perioperative analgesia. Total knee arthroplasty (TKA) is associated with significant postoperative pain. Cytokines contribute to the pathophysiology of osteoarthritis (OA) and associated pain. However, the influence of perioperative cytokine levels after TKA surgery upon postoperative pain remains unexplored. METHODS: We designed a prospective observational study to profile three proinflammatory cytokines, interleukin-6 (IL-6), tumor necrosis factor α (TNFα), and leptin in serum, synovial, and cerebrospinal fluid of TKA patients perioperatively to determine associations between cytokine levels and pain. We characterized time-trajectories in cytokines pre- and post-surgery and explored their relationships to pain across gender. RESULTS: Preoperative pain, measured by functional pain disability scores (PDQ), was predictive of postoperative pain. There were no gender differences in severity of preoperative pain or acute postoperative pain. Serum IL-6, serum leptin, and synovial fluid leptin were positively correlated with body mass index and preoperative pain severity. Stratification of patients by gender revealed strong correlations between serum IL-6, leptin, and PDQ only in females, suggesting that females may be more sensitive to the nociceptive actions of these cytokines. Although serum IL-6 increased dramatically (and TNFα increased modestly) four hours after surgery and remained elevated at 72h; they were not associated with the severity of acute postoperative pain. CONCLUSIONS: Our data suggest that while preoperative chronic pain is predictive of the severity of acute postoperative pain in TKA patients, the pre- and post-operative inflammatory status does not predict postoperative pain.

Association of postoperative nausea/vomiting and pain with breastfeeding success.

BACKGROUND: Successful breastfeeding is a goal set forth by the World Health Organization to improve neonatal care. Increasingly, patients express the desire to breastfeed, and clinicians should facilitate successful breastfeeding. The primary aim of this study is to determine if postoperative nausea and vomiting (PONV) or postoperative pain are associated with decreased breastfeeding success after cesarean delivery. METHODS: This is a historical cohort study using the Stony Brook Elective Cesarean Delivery Database. Self-reported breastfeeding success at 4 weeks postoperative was analyzed for associations with postoperative antiemetic use and postoperative pain scores. Breastfeeding success was also analyzed for associations with patient factors and anesthetic medications. RESULTS: Overall, 86% of patients (n = 81) who intended on breastfeeding reported breastfeeding success. Breastfeeding success was not associated with postoperative nausea or vomiting as measured by post anesthesia care unit antiemetic use (15% use in successful vs. 18% use in unsuccessful, p = 0.67) or 48-h antiemetic use (28% use in successful group vs 36% use in unsuccessful group, p = 0.732). Pain visual analog scale scores at 6, 12 and 24 h postoperatively were not significantly different between patients with or without breastfeeding success. Breastfeeding success was associated with having had at least 1 previous child (86% vs 36%, p < 0.001). Patients with asthma were less likely to have breastfeeding success (45% vs 4%, p = 0.002). CONCLUSIONS: Efforts to improve PONV and pain after cesarean delivery may not be effective in improving breastfeeding success. To possibly improve breastfeeding rates, resources should be directed toward patients with no previous children and patients with asthma.

Feedback Simulation for Acupressure Training and Skill Assessment.

INTRODUCTION: Previous acupressure studies have yielded varying results. This could be due to differences in the amount of pressure applied to the acupressure point (acupoint) by study personnel within a study as well as between studies. Standardizing the level of pressure applied at an acupoint could improve clinical care and future research. METHODS: As part of an ongoing randomized clinical trial of postoperative acupressure, five trainees were asked to perform 2 minutes of acupressure and light touch sessions on a simulator. The applied weight was recorded every minute. Individual skill assessment was performed using cumulative sum analysis. Six pretraining and 20 posttraining measurements in each acupressure and light touch group were compared with an expert's simulation values. RESULTS: Before training (baseline), there was significant difference in applied weight (grams) between the expert [5705 (636)] and five trainees [2998 (798), P = 0.004]. Four of the five trainees crossed the lower decision limit assessing proficiency in the acupressure group, and all five trainees were successful in the light touch group. The trainees' average number of measurements needed to cross the lower decision limit (H0), that is, defining that an individual failure rate does not statistically differ from the acceptable failure rate, was 21.3 measurements for acupressure. After this feedback simulation, trainees' scores showed no significant difference (P > 0.05) when assessed against the expert. CONCLUSIONS: Feedback simulation for acupressure training and skill assessment, evaluated by cumulative sum analysis, may help in improving the standardization of acupressure therapy performed during clinical practice or research.

Leptin levels are negatively correlated with 2-arachidonoylglycerol in the cerebrospinal fluid of patients with osteoarthritis.

BACKGROUND: There is compelling evidence in humans that peripheral endocannabinoid signaling is disrupted in obesity. However, little is known about the corresponding central signaling. Here, we have investigated the relationship between gender, leptin, body mass index (BMI) and levels of the endocannabinoids anandamide (AEA) and 2-arachidonoylglycerol (2-AG) in the serum and cerebrospinal fluid (CSF) of primarily overweight to obese patients with osteoarthritis. METHODOLOGY/PRINCIPAL FINDINGS: Patients (20 females, 15 males, age range 44-78 years, BMI range 24-42) undergoing total knee arthroplasty for end-stage osteoarthritis were recruited for the study. Endocannabinoids were quantified by liquid chromatography - mass spectrometry. AEA and 2-AG levels in the serum and CSF did not correlate with either age or BMI. However, 2-AG levels in the CSF, but not serum, correlated negatively with CSF leptin levels (Spearman's ρ -0.48, P=0.0076, n=30). No such correlations were observed for AEA and leptin. CONCLUSIONS/SIGNIFICANCE: In the patient sample investigated, there is a negative association between 2-AG and leptin levels in the CSF. This is consistent with pre-clinical studies in animals, demonstrating that leptin controls the levels of hypothalamic endocannabinoids that regulate feeding behavior.