Hyperthermic intraperitoneal chemotherapy enhances blood coagulation perioperatively evaluated by thromboelastography: a pilot study.

Background and Objectives: Postoperative thromboembolism is a significant cause of prolonged recovery in patients undergoing cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Thromboelastography (TEG) can detect hypercoagulable states and predict thromboembolic complications after surgery. This study assessed the impact of CRS and HIPEC on TEG values.Methods: TEG parameters reaction time (R), kinetics time (K), angle (α), maximum amplitude (MA), and lysis percent at 60 min (LY60) were determined preoperatively, and at the end of CRS, during HIPEC, and at the end of the operation using blood samples from 15 HIPEC patients. Platelets, P-TT, and aPTT were also determined before and after CRS.Results: A total of 75 samples were analyzed. During CRS, there was a significant reduction in the mean MA (3.06 mm, p = 0.001). The mean P-TT declined by 32% (p < 0.001) and mean platelets by 55 × 109/L (p < 0.001). During HIPEC, the mean R and K shortened by 1.04 min (p = 0.015) and 0.18 min (p = 0.018), respectively, whereas α increased by 2.48° (p = 0.005).Conclusions: During CRS, both TEG and conventional laboratory tests indicated hypocoagulation. During HIPEC, however, the initiation of coagulation and the kinetics of thrombin formation were accelerated.

Swallowing-related quality of life after free flap surgery due to cancer of the head and neck.

PURPOSE: Treatment of head and neck cancers (HNC) often leads to impairment in speech and swallowing functions. This study evaluated swallowing problems and the impact of complications on swallowing-related QOL after free flap surgery for HNC. METHODS: Swallowing-related QOL was assessed using MDADI and SWAL questionnaires. RESULTS: Of 45 assessed patients, 25 (45.5%) had at least one postoperative complication. Patients reported less than < 86 points in 8/9 SWAL-QOL domains. The SWAL-QL total score or MDADI composite scores were not related to surgical complications. Those with medical complications had lower scores in SWAL-QOL domains of mental health (82.8 (21.8) vs 65.5 (24.2), p = 0.024) and sleep (77.6 (23.0) vs 52.3 (24.3), p = 0.003). CONCLUSIONS: In conclusion, swallowing related QOL is significantly impaired after 2 years of the tumor resection and free flap reconstruction for cancer of the head and neck, when using the cut-off value of 86 points in SWAL-QOL assessment tool. Surgical complications did not have an impact on swallowing-related QOL but medical complications were related to impairment in general QOL-related domains.

Quality of life after free flap surgery for cancer of the head and neck in patients with or without postoperative complications.

BACKGROUND: Despite advances in surgical techniques, postoperative complications are frequent after free flap surgery for cancer of the head and neck. The present study assessed quality of life (QOL) in patients with and without postoperative complications. METHODS: QOL was evaluated using RAND-36, EORTC-C30 and H&N-35, and UW-QOL questionnaires. RESULTS: Of 53 assessed patients, 29 (54.7%) had at least one complication. Those with medical complications (n = 12, 22.6%) had significantly lower QOL in all domains of RAND-36 except emotional well-being. They also reported lower scores in EORTC-C30 domains of financial difficulties, pain, and insomnia and UW-QOL domains of pain, activity, and recreation. The QOL for patients without complications was comparable to the general population. CONCLUSION: QOL after free flap surgery for cancer of the head and neck is reduced in patients with postoperative medical complications.

Hepatitis E Virus in Finland: Epidemiology and Risk in Blood Donors and in the General Population.

Autochthonous hepatitis E (HEV) cases have been increasingly recognized and reported in Europe, caused predominantly by the zoonotic HEV genotype 3. The clinical picture is highly variable, from asymptomatic to acute severe or prolonged hepatitis in immunocompromised patients. The main route of transmission to humans in Europe is the ingestion of undercooked pork meat. Transfusion-transmitted HEV infections have also been reported. The aim of the study was to determine the HEV epidemiology and risk in the Finnish blood donor population. A total of 23,137 samples from Finnish blood donors were screened for HEV RNA from individual samples and 1012 samples for HEV antibodies. Additionally, laboratory-confirmed hepatitis E cases in 2016-2022 were extracted from national surveillance data. The HEV RNA prevalence data was used to estimate the risk of transfusion transmission of HEV in the Finnish blood transfusion setting. Four HEV RNA-positive were found, resulting in 1:5784 (0.02%) RNA prevalence. All HEV RNA-positive samples were IgM-negative, and genotyped samples represented genotype HEV 3c. HEV IgG seroprevalence was 7.4%. From the HEV RNA rate found in this study and data on blood component usage in Finland in 2020, the risk estimate for a severe transfusion-transmitted HEV infection is 1:1,377,000 components or one in every 6-7 years. In conclusion, the results indicate that the risk of transfusion-transmitted HEV (HEV TTI) in Finland is low. However, continuous follow-up of the HEV epidemiology in relation to the transfusion risk landscape in Finland is necessary, as well as promoting awareness in the medical community of the small risk for HEV TTI, especially for immunocompromised patients.

The duration of residual neuromuscular block after administration of neostigmine or sugammadex at two visible twitches during train-of-four monitoring.

BACKGROUND: Adequate recovery from neuromuscular block (NMB) is imperative for the patient to have full control of pharyngeal and respiratory muscles. The train-of-4 (TOF) ratio should return to at least 0.90 to exclude potentially clinically significant postoperative residual block. Fade cannot be detected reliably with a peripheral nerve stimulator (PNS) at a TOF ratio >0.4. The time gap between loss of visual fade by using a PNS until objective TOF ratio has returned to >0.90 can be considered "the potentially unsafe period of recovery." According to our hypothesis the duration of this period would be significantly shorter with sugammadex than with neostigmine. METHODS: Fifty patients received volatile anesthetics, opioids, and a rocuronium-induced NMB. TOF-Watch without a preload was used, but the anesthesiologist relied on visual evaluation of the TOF responses only. At end of operation, patients were randomized to receive either neostigmine 50 µg/kg or sugammadex 2 mg/kg, when 2 twitch responses were detected after the last dose of rocuronium. Timing of tracheal extubation was based on PNS and clinical data. Duration of the potentially unsafe period of recovery after reversal by either neostigmine or sugammadex was analyzed. Mann-Whitney U test and Pearson χ(2) test were used for statistical analysis. RESULTS: The times [mean ± sd (range)] from loss of visual fade to TOF ratio >0.90 were 10.3 ± 5.5 (1.3 to 26.0) minutes and 0.3 ± 0.3 (0.0 to 1.0) minutes in the neostigmine and sugammadex groups, respectively (P < 0.001). The times from reversal by neostigmine or sugammadex to TOF ratio >0.90 were 13.3 ± 5.7 (3.5 to 28.9) and 1.7 ± 0.7 (0.7 to 3.5) minutes, respectively (P < 0.001). The values of TOF ratios at the time of loss of visual fade were 0.34 ± 0.14 (0.00 to 0.56) in patients given neostigmine and 0.86 ± 0.11 (0.64 to 1.04) in patients given sugammadex (P < 0.001). CONCLUSIONS: There is a significant time gap between visual loss of fade and return of TOF ratio >0.90 after reversal of a rocuronium block by neostigmine. Sugammadex in comparison with neostigmine allows a safer reversal of a moderate NMB when relying on visual evaluation of the TOF response.

Thromboelastography Values Remain Hypercoagulative 6 Months After Obesity Surgery: a Pilot Study.

PURPOSE: Obesity causes a prothrombotic state and is known as a predisposing factor for thromboembolic events. In this pilot study, we assessed the impact of surgery for obesity and the subsequent weight loss on blood coagulation using traditional coagulation tests and thromboelastography (TEG). MATERIAL AND METHODS: We studied blood samples from 18 patients receiving bariatric surgery. Besides traditional blood coagulation tests and high-sensitivity C-reactive protein (hsCRP) as a marker of inflammation, the TEG parameters reaction time (R), kinetics time (K), angle (α), maximum amplitude (MA), clot strength (G), and lysis percent at 60 min (LY60) were determined preoperatively and on the first postoperative day and 6 months after surgery. RESULTS: Altogether, 54 samples were analyzed. The median MA (71.3 mm), G (12,403.3 d/sc), and hsCRP (3.5 mg/l) were elevated preoperatively. The median hsCRP further increased on the first day postoperatively, but declined to the normal range 6 months after surgery, while MA and G remained elevated. In traditional coagulation tests, there was an increase in median fibrinogen and D-dimer postoperatively. D-dimer normalized (0.4 mg/l) during the study period, while the fibrinogen level (4.1 g/l) remained above the upper limit of normal. CONCLUSIONS: Measured by TEG, patients receiving bariatric surgery have hemostatic abnormalities indicating hypercoagulation at the 6-month follow-up visit, suggesting an elevated risk for thromboembolic events for at least 6 months after surgery.

Tight junction proteins in gallbladder epithelium: different expression in acute acalculous and calculous cholecystitis.

There is a paucity of information of tight junction (TJ) proteins in gallbladder epithelium, and disturbances in the structure of these proteins may play a role in the pathogenesis of acute acalculous cholecystitis (AAC) and acute calculous cholecystitis (ACC). Using immunohistochemistry, we investigated the expression of TJ proteins claudin-1, -2, -3, and -4, occludin, zonula occludens (ZO-1), and E-cadherin in 9 normal gallbladders, 30 gallbladders with AAC, and 21 gallbladders with ACC. The number of positive epithelial and endothelial cells and the intensity of the immunoreaction were determined. Membrane-bound and cytoplasmic immunoreactivities were separately assessed. We found that TJ proteins were uniformly expressed in normal gallbladder epithelium, with the exception of claudin-2, which was present in less than half of the cells. In AAC, expression of cytoplasmic occludin and claudin-1 were decreased, as compared with normal gallbladder. In ACC, expression of claudin-2 was increased, and expression of claudin-1, -3, and -4, occludin, and ZO-1 were decreased, as compared with normal gallbladder or AAC. We conclude that there are significant differences in expression of TJ proteins in AAC and ACC, supporting the idea that AAC represents a manifestation of systemic inflammatory disease, whereas ACC is a local inflammatory and often infectious disease.

Goal-directed fluid management in free flap surgery for cancer of the head and neck.

BACKGROUND: Goal-directed fluid management using stroke volume variation (SVV) analysis is not well studied in free flap reconstruction surgery in patients with head and neck cancer. METHODS: Patients operated due to cancer of the head and neck with free flap reconstruction during 2008-2010 and 2012-2014 in Oulu University Hospital were retrospectively evaluated to determine the impact of SVV-guided fluid management on perioperative fluid balance, postoperative complications and hospital length of stay (LOS). RESULTS: A total of 104 patients were included in the study and in 48 of them SVV was used to guide intraoperative fluid management. The SVV-guided fluid management led to significant reduction in intraoperative fluid load (6070 mL vs. 8185 mL) and hospital length of stay (11.5 vs. 14.0 days). There was no difference in the number of postoperative complications between the groups. CONCLUSIONS: The SVV-guided fluid management reduces fluid administration in free flap reconstruction surgery with head and neck cancer.

Fructose-1,6-bisphosphate supports cerebral energy metabolism in pigs after ischemic brain injury caused by experimental particle embolization.

BACKGROUND: Fructose-1,6-bisphosphate (FDP) is a high-energy intermediate that enhances glycolysis, preserves cellular adenosine triphosphate stores, and prevents the increase of intracellular calcium in ischemic tissue. Since it has been shown to provide metabolic support to the brain during ischemia, we planned this study to evaluate whether FDP is neuroprotective in the setting of combining hypothermic circulatory arrest (HCA) and irreversible embolic brain ischemic injury. METHODS: Twenty pigs were randomly assigned to receive 2 intravenous infusions of either FDP (500 mg/kg) or saline. The first infusion was given just before a 25-minute period of HCA and the second infusion immediately after HCA. Immediately before HCA, the descending aorta was clamped and 200 mg of albumin-coated polystyrene microspheres (250-750 mm in diameter) were injected into the isolated aortic arch in both study groups. RESULTS: There were no significant differences between the study groups in terms of neurological outcome. Brain lactate/pyruvate ratio was significantly lower (P = .015) and brain pyruvate levels (P = .013) were significantly higher in the FDP group compared with controls. Brain lactate levels were significantly higher 8 hours after HCA (P = .049). CONCLUSION: The administration of FDP before and immediately after HCA combined with embolic brain ischemic injury was associated with significantly lower brain lactate/pyruvate ratio and significantly higher levels of brain pyruvate, as well as lower lactate levels 8 hours after HCA. FDP seems to protect the brain by supporting energy metabolism. The neurological outcome was not improved, most likely resulting from the irreversible nature of the microsphere occlusion.

Propofol is associated with impaired brain metabolism during hypothermic circulatory arrest: an experimental microdialysis study.

BACKGROUND: Propofol is a widely used anesthetic in cardiac surgery. It has been shown to increase cerebrovascular resistance resulting in decreased cerebral blood flow. Efficient brain perfusion and tissue oxygenation during cardiopulmonary bypass (CPB) is essential in surgery requiring hypothermic circulatory arrest (HCA). The effects of propofol on brain metabolism are reported in a surviving porcine model of HCA. METHODS: Twenty female juvenile pigs undergoing 75 minutes of HCA at a brain temperature of 18 degrees C were assigned to either propofol- or isoflurane anesthesia combined with alpha-stat perfusion strategy during CPB cooling and rewarming. Brain microdialysis analysis was used for determination of brain metabolism, and tissue oxygen partial pressure and intracranial pressures were also followed-up until 8 hours postoperatively. RESULTS: Brain concentrations of glutamate and glycerol were significantly higher in the propofol group throughout the experiment (P < .01 and P < .01, respectively). The lactate/pyruvate ratio was significantly higher in the propofol group at 6-, 7-, and 8-hour intervals (P < .05, P < .01, and P < .05, respectively). The intracranial pressure was significantly higher at the 8-hour postoperative interval (P < .05) in the propofol group. A trend toward higher brain oxygen concentrations was observed in the isoflurane group. CONCLUSIONS: Anesthesia with propofol as compared with isoflurane is associated with impaired brain metabolism during experimental HCA.

Aprotinin to improve cerebral outcome after hypothermic circulatory arrest: a study in a surviving porcine model.

BACKGROUND: Aprotinin is a serine protease inhibitor, which is usually used during cardiac surgery to reduce blood loss. There is evidence that aprotinin has neuroprotective effects during ischemia. We planned this study to evaluate its potential neuroprotective efficacy during hypothermic circulatory arrest (HCA). METHODS: Twenty piglets with a median weight of 25.7 kg (interquartile range, 23.9-26.6) were randomly assigned to receive aprotinin or placebo prior to a 75-minute period of HCA at 18 degrees C. Brain microdialysis parameters and neurological and histological scores were the primary outcome measures. RESULTS: Changes in brain metabolic parameters and histopathological findings were favorable in the aprotinin group. Brain lactate concentrations were significantly lower in the aprotinin group during the experiment (P = .02) along with blood lactate concentrations in the aprotinin group (P = .023). Brain glucose was significantly higher during the experiment (P = 0.02). Intracranial pressure tended to be higher in the control group. Two of 10 animals in the aprotinin group and 4 of 10 in the control group failed to reach full recovery on the seventh postoperative day. Four animals of 10 in the aprotinin group and 6 animals of 10 in the control group had brain infarction (P = .40). CONCLUSIONS: The present data suggest that aprotinin mitigates cerebral damage and improves neurological outcome following a period of HCA.

Effects of pH management during selective antegrade cerebral perfusion on cerebral microcirculation and metabolism: alpha-stat versus pH-stat.

BACKGROUND: Selective cerebral perfusion (SCP) is used for extending the period during which surgical procedures can be safely performed. We sought to determine the direct effects of pH management on cerebral microcirculation and metabolism during SCP. METHODS: An experimental SCP porcine model was created by selectively allowing cold perfusate only into the bicarotid brachiocephalic trunk during the SCP period. Twenty-four piglets (6 to 8 weeks; mean weight, 26.1 +/- 4.1 kg) underwent 15-minute normothermic cardiopulmonary bypass, 45-minute cooling cardiopulmonary bypass, 60-minute SCP at 25 degrees C, and 45-minute rewarming cardiopulmonary bypass with either alpha-stat or pH-stat perfusion strategy randomly assigned. A cranial window was created over the parietal cortex for visualization of the cerebral vessels with intravital microscopy. Rhodamine-stained leukocytes were observed in cerebral postcapillary venules for adhesion and rolling. Microdialysis analysis was used for determination of brain metabolism. RESULTS: Brain concentration of lactate was significantly higher in the alpha-stat group at 45 minutes of SCP, and at 15- and 45-minute rewarming intervals (p = 0.03; p = 0.003; and p = 0.05; respectively), reaching borderline statistical significance when assessed throughout the experiment (p = 0.06 for differences between groups). Further, at the end of cooling, the oxygen delivery tended to be higher in the pH-stat group (p = 0.07), whereas at the 30-minute rewarming interval, the oxygen extraction tended to be higher in the alpha-stat group (p = 0.06). There were no statistically significant differences between the groups in leukocyte-endothelial interaction, arterial diameter, or tissue oxygenation. CONCLUSIONS: The higher concentration of brain lactate and the tendency to higher oxygen extraction levels during rewarming with alpha-stat strategy suggests anaerobic metabolism occurred during SCP. No major differences between pH management strategies in cerebral microcirculation could be shown during SCP.

Leukocyte filtration to decrease the number of adherent leukocytes in the cerebral microcirculation after a period of deep hypothermic circulatory arrest.

OBJECTIVE: Cardiopulmonary bypass and hypothermic circulatory arrest induce a systemic inflammatory response, including a cascade of leukocyte and endothelial cell activity, during the postischemic reperfusion phase. Accumulation of leukocytes in the brain can lead to neurologic problems after cardiac surgery. The beneficial effects of a leukocyte-depleting filter have been documented, but because of contradictory results the underlying function of the filter remains unclear. METHODS: Twenty-two juvenile piglets (6 to 8 weeks) were randomly assigned to undergo cardiopulmonary bypass with or without a leukocyte-depleting filter 60 minutes before and 60 minutes after a 75-minute hypothermic circulatory arrest at 18 degrees C. The cerebral vessels were visualized with intravital microscopy through a cranial window placed over the parietal cortex. Rhodamine staining was used to observe adherent and rolling leukocytes in the cerebral postcapillary venules. The animals were electively killed 1 hour after weaning from cardiopulmonary bypass. RESULTS: There were no significant differences between the study groups regarding hemodynamic data. Numbers of adherent activated leukocytes were lower in the leukocyte filtration group, reaching borderline statistical significance when assessed throughout the experiment (between-groups P = .069) and actual statistical significance when assessed during the rewarming period (between-groups P = .029). CONCLUSION: The leukocyte-depleting filter succeeded in reducing the number of adherent leukocytes during the reperfusion period in an experimental operation with deep hypothermic circulatory arrest. Such a filter thus could mitigate cerebral reperfusion injury after cardiac surgery.

Hypertonic saline dextran improves outcome after hypothermic circulatory arrest: a study in a surviving porcine model.

BACKGROUND: Hypertonic saline dextran (HSD) has been shown to have neuroprotective properties. In the present study we have assessed its potential neuroprotective efficacy in the setting of hypothermic circulatory arrest in a surviving porcine model. METHODS: Twenty-four pigs were randomized to receive two 5-minute intravenous infusions (4 mL/kg) of either HSD (7.5 % saline, 6% dextran 70) or normal saline immediately after and 4 hours after a 75-minute period of hypothermic circulatory arrest at a brain temperature of 18 degrees C. RESULTS: The 7-day survival was 75% in the HSD group and 66% in the control group (p > 0.9). Brain total histopathologic score was lower in the HSD group (p = 0.01). Postoperative behavioral scores were higher in the HSD group on the second day after surgery (p = 0.03). Intracranial pressure was lower in the HSD group from 45 minutes to 8 hours after hypothermic circulatory arrest (p = 0.03). Cerebral perfusion pressure was higher in the HSD group from 45 minutes to 3 hours after hypothermic circulatory arrest (p = 0.06). Brain lactate concentration was lower in the HSD group when compared with controls (p = 0.05). Furthermore, brain glucose levels tended to be higher and brain lactate-pyruvate ratio and lactate-glucose ratio were lower in the HSD group. Brain tissue oxygen partial pressures were somewhat higher in the HSD group (p = 0.08). CONCLUSIONS: The use of HSD in experimental hypothermic circulatory arrest is associated with significantly better neurologic recovery, better histopathology, lower intracranial pressure, higher cerebral perfusion pressure, and better preservation of brain metabolism.

pH-stat versus alpha-stat acid-base management strategy during hypothermic circulatory arrest combined with embolic brain injury.

BACKGROUND: There is some evidence of beneficial metabolic effects associated with the pH-stat than with alpha-stat perfusion strategy, but this is tempered by a likely increased risk of embolism to the brain, especially in adult patients. We investigated this possible adverse effect in an experimental model that combined hypothermic circulatory arrest (HCA) and embolic brain injury. METHODS: Twenty-four female juvenile pigs undergoing 25 minutes of HCA at a brain temperature of 18 degrees C were assigned to either alpha-stat (n = 12) or pH-stat (n = 12) strategy during cardiopulmonary bypass. Before the initiation of HCA, the descending aorta was clamped and 200 mg of albumin-coated polystyrene microspheres (250 to 750 microm in diameter) were injected into the isolated aortic arch in both groups. RESULTS: The 7-day survival rate was 75% in the pH-stat group and 50% in the alpha-stat group (p = 0.40). The pH-stat group had significantly better behavioral scores on postoperative days 5 (p = 0.03) and 6 (p = 0.04). The pH-stat strategy was associated with better postoperative intracranial pressures and histopathologic scores, but such differences did not reach statistical significance. The alpha-stat group had lower brain glucose concentrations postoperatively as well as higher brain lactate/glucose and lactate/pyruvate ratios CONCLUSIONS: These results suggest that pH-stat strategy does not cause any worse brain injury than the alpha-stat strategy. Indeed, the pH-stat strategy is associated with a slightly better outcome compared with the alpha-stat strategy, even in the setting of cerebral embolization. This observation suggests that the pH-stat strategy could also be used in adults during deep hypothermic cardiopulmonary bypass despite the increased risk of intraoperative cerebral embolization.

Apotransferrin, C1-esterase inhibitor, and alpha 1-acid glycoprotein for cerebral protection during experimental hypothermic circulatory arrest.

BACKGROUND: Because of current limitations in improving metabolic support to the brain during hypothermic circulatory arrest (HCA), attenuation of ischemia-reperfusion injury remains an area of therapeutic intervention of relevance. Apotransferrin (Apo-Tf), alpha 1-acid glycoprotein (AGP), and C1-esterase inhibitor (C1-INH) have been herein evaluated as potential beneficial agents in reducing the ischemia-reperfusion injury in a surviving model of HCA. METHODS: Apo-Tf 100 mg/kg (n = 6), C1-INH 50 IU/kg (n = 6), AGP 100 mg/kg (n = 6), or NaCl 0.9% 2 ml/kg (n = 6) were randomly administered to 24 juvenile pigs after a 75-min period HCA at a brain temperature of 18 degrees C. RESULTS: Animals in the Apo-Tf group had a slightly better 7-day survival (66.7%) compared with the other study groups (50%), but such a difference was not statistically significant. Some favorable changes in the brain glucose metabolism parameters were observed in the AGP, C1-INH, and Apo-Tf groups, but these did not reach statistical significance. Semiquantitative analysis of the histopathological findings did not show any significant difference between the study groups. However, only two out of four surviving animals in the Apo-Tf group developed brain infarction, whereas all three survivors of the remaining study groups developed brain infarction. CONCLUSIONS: Although the small size of the study groups may affect the present findings, none of the metabolic and hemodynamic parameters as well as outcome endpoints indicate a substantial therapeutic efficacy of Apo-Tf, AGP, and C1-INH as neuroprotective agents after experimental HCA.