Bleeding and hemostasis during normo- and hypothermia : Studies on porcine and rat models

Background: Numerous animal studies have shown protective effects of hypothermia (HT) on hemorrhagic shock. These findings do not correlate with clinical findings, were studies on trauma registers have shown that HT is an independent factor of death when associated with trauma. HT affects hemostasis, but is just one of many factors that cause the coagulopathy often seen in trauma patients with uncontrolled bleedings. To what extent HT per se contributes to the hemorrhage and hence, the deterioration of shock is virtually unknown. In this thesis we investigate HTs impact on uncontrolled hemorrhage, but also if rebleeding volumes could be affected by hemostatic drugs or different resuscitation regimes. Methods: I: 18 pigs were randomized to HT (n = 10) or normothermia (NT) (n = 8). A volume controlled hemorrhagic shock was induced by a 40 % exsanguination of estimated blood volume (EBV). HT animals were cooled to 32.5 degrees C and rewarmed again after 2 hours. The observation time (OT) was 420 minutes. II: 23 pigs were randomized to receive tranexamic acid (n = 11) or placebo (n = 12). Uncontrolled hemorrhage was induced by lacerating the aorta, producing an exsanguination estimated to 35 40 % of EBV. These animals were not actively cooled. Rebleeding events were monitored by ultrasonic probes. OT was 130 minutes. Thrombelastography (TEG) was used to evaluate coagulation changes in study I and II. III: 40 rats were randomized to HT (n = 20) or NT (n = 20). Uncontrolled hemorrhage was induced by puncturing the femoral artery, producing an exsanguination estimated to 24 % of EBV. HT animals were cooled to 30 degrees C and rewarmed again at 90 minutes. The incidence, on-set time, duration and volume of rebleedings were followed. OT was 180 minutes. IV: 60 rats, all cooled and processed according to the protocol of study III, were randomized to 3 different resuscitation groups; Low (LRe), Medium (MRe) or High (HRe) or Medium resuscitation +Desmopressin (MRe + D) (n = 4 x 15). Results: I: HT induced a coagulopathy apparent at temperatures < 35degrees C, and reversible upon rewarming. There were no differences in hemodynamics, blood chemistry and mortality between groups at the end of the study period. II: There were no differences in rebleeding or mortality between the tranexamic acid and placebo groups. Non- survivors had significantly higher rebleeding volumes compared to survivors. At the end of observation, there was a strong correlation between an aggravated coagulopathy, as measured by TEG, and total bleeding volumes. III: HT animals had significantly higher rebleeding volumes (HT = 43 % vs. NT = 3 % of EBV). Rebleeding volumes were larger in the HT group even at temperatures > 35 degrees C. Much higher blood pressure, induced by cooling, was seen in the HT group. IV: There were significantly higher rebleeding volumes in the HRe group and a trend towards higher mortality in the LRe group. No significant differences in the number or volume of rebleeding and no difference in mortality between the MRe + D and MRe groups was seen. Conclusions: HT induces a coagulopathy that is reversible upon rewarming. During trauma and uncontrolled hemorrhage, other factors than HT contribute to this coagulopathy. Hemodynamic changes provoked by cooling and HT, i.e. a rise in blood pressure, contribute to repeated rebleeding and hence, continuous hemorrhage. An MRe resuscitation regime seems most beneficial for outcome during HT and uncontrolled hemorrhage. Tranexamic acid at NT and desmopressin at HT conditions does not reduce rebleeding in penetrating trauma with uncontrolled hemorrhage

The impact of the type of lake catchment on the mercury content in perche

Raita Čilipāna maģistra darbs “Ezera sateces baseina tipa ietekme uz dzīvsudraba saturu asaros”. Maģistra darba mērķis ir izvērtēt ezera sateces baseina ietekmi uz dzīvsudraba saturu asaros. Maģistra darbā tika kvantitatīvi noteikts dzīvsudraba saturs Liepājas ezera, Ķīšezera, Burtnieka un Alūksnes ezerā mītošajos asaru muskuļaudos, izmantojot atomu absorbcijas spektrometrijas metodes. Literatūras apskatā ir apkopota informācija par dzīvsudraba ietekmi uz cilvēka organismu, galvenajiem dzīvsudraba dabiskās emisijas un antropogēnās emisijas avotiem. Veikta pētījumā apskatīto ezeru aprakstu izveide, aprakstot to sateces baseinā esošos potenciālos piesārņotājus un tā struktūru. Atslēgas vārdi: Dzīvsudrabs, asaris, Ķīšezers, Burtnieks, Alūksnes ezers, Liepājas ezers, ezera sateces baseinsRaitis Čilipān`s the title of master work thesis "The impact of the type of lake catchment on the mercury content in perche." Master thesis aims to assess the The impact of the type of lake catchment on the mercury content in perche. The content of mercury was quantified in the master's thesis using atomic absorption spectrometry methods on the muscle tissues of perch found in the following lakes: Liepāja, Ķīšezers, Burtnieks and Alūksne. The literature review summarizes the effects of mercury on the human body, the main sources of natural mercury emissions and anthropogenic emissions. The description of the lakes researched in this study outlines the potential contaminants in the catchment area and its structure. Keywords: Mercury, perche, Ķīšezers, Burtnieks, Alūksnes ezers, Liepājas ezers, lake catchmen

Effects of Different Fluid Regimes and Desmopressin on Uncontrolled Hemorrhage During Hypothermia in the Rat

Resuscitation with large volumes of crystalloids during traumatic hemorrhagic shock might increase the mortality by inducing rebleeding. However, few studies have addressed this problem during hypothermic conditions. Sixty-eight Sprague-Dawley rats were exposed to a standardized femoral artery injury and resuscitated with low (LRe), medium (MRe), or high (HRe) intensity using lactated Ringer's solution after being cooled to 30°C. An additional MRe group was also given desmopressin since this drug might reverse hypothermic-induced impairment of the primary hemostasis. The rats were rewarmed after 90 minutes and observed for 3 hours. The incidence, on-set time, duration, and volume of bleedings and hemodynamic changes were recorded. Rebleedings occurred in 60% of all animals and were more voluminous in the HRe group than in the LRe group (p=0.01). The total rebleeding volume per animal increased with the rate of fluid administration (r=0.50, p=0.01) and the duration of each rebleeding episode was longer in the HRe group than in the LRe group (p&lt;0.001). However, the mortality tended to be higher in the LRe group (LRe=6/15, MRe=1/15, HRe=2/15, p=0.07). Desmopressin did not change the bled volume or the mortality. Overall, the mortality increased if rebleeding occurred (10/35 rebleeders died vs. 1/25 nonrebleeders, p=0.015). Liberal fluid administration increased the rebleeding volume while a trend toward higher mortality was seen with the restrictive fluid program. Desmopressin had no effect on the studied parameters

Global variation in postoperative mortality and complications after cancer surgery: a multicentre, prospective cohort study in 82 countries

© 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 licenseBackground: 80% of individuals with cancer will require a surgical procedure, yet little comparative data exist on early outcomes in low-income and middle-income countries (LMICs). We compared postoperative outcomes in breast, colorectal, and gastric cancer surgery in hospitals worldwide, focusing on the effect of disease stage and complications on postoperative mortality. Methods: This was a multicentre, international prospective cohort study of consecutive adult patients undergoing surgery for primary breast, colorectal, or gastric cancer requiring a skin incision done under general or neuraxial anaesthesia. The primary outcome was death or major complication within 30 days of surgery. Multilevel logistic regression determined relationships within three-level nested models of patients within hospitals and countries. Hospital-level infrastructure effects were explored with three-way mediation analyses. This study was registered with ClinicalTrials.gov, NCT03471494. Findings: Between April 1, 2018, and Jan 31, 2019, we enrolled 15 958 patients from 428 hospitals in 82 countries (high income 9106 patients, 31 countries; upper-middle income 2721 patients, 23 countries; or lower-middle income 4131 patients, 28 countries). Patients in LMICs presented with more advanced disease compared with patients in high-income countries. 30-day mortality was higher for gastric cancer in low-income or lower-middle-income countries (adjusted odds ratio 3·72, 95% CI 1·70–8·16) and for colorectal cancer in low-income or lower-middle-income countries (4·59, 2·39–8·80) and upper-middle-income countries (2·06, 1·11–3·83). No difference in 30-day mortality was seen in breast cancer. The proportion of patients who died after a major complication was greatest in low-income or lower-middle-income countries (6·15, 3·26–11·59) and upper-middle-income countries (3·89, 2·08–7·29). Postoperative death after complications was partly explained by patient factors (60%) and partly by hospital or country (40%). The absence of consistently available postoperative care facilities was associated with seven to 10 more deaths per 100 major complications in LMICs. Cancer stage alone explained little of the early variation in mortality or postoperative complications. Interpretation: Higher levels of mortality after cancer surgery in LMICs was not fully explained by later presentation of disease. The capacity to rescue patients from surgical complications is a tangible opportunity for meaningful intervention. Early death after cancer surgery might be reduced by policies focusing on strengthening perioperative care systems to detect and intervene in common complications. Funding: National Institute for Health Research Global Health Research Unit

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

© 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licenseBackground: Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide. Methods: A multimethods analysis was performed as part of the GlobalSurg 3 study—a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital. Findings: Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3·85 [95% CI 2·58–5·75]; p<0·0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63·0% vs 82·7%; OR 0·35 [0·23–0·53]; p<0·0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer. Interpretation: Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised. Funding: National Institute for Health and Care Research