Induced Moderate Hypothermia in Aortic Rupture With Retroperitoneal Bleeding: A Randomized Porcine Study.

OBJECTIVE: Induced hypothermia improves outcome in aortic arch surgery, neonatal neurointensive care, and transplant surgery for example. In contrast, spontaneous hypothermia has been associated with worse outcomes in patients suffering from hemorrhagic shock, mostly explained by its adverse effects on the coagulation system. We investigated if induced hypothermia would impair short-term survival in experimental aortic rupture with retroperitoneal bleeding. METHODS: Anesthetized pigs were randomized into 2 groups: hypothermia by peritoneal lavage of ice-cold Ringer's acetate and external cooling (n = 10) and normothermia (n = 10). Aortic rupture with retroperitoneal bleeding was induced by endovascular means creating a 6 mm hole in the retroperitoneal portion of abdominal aorta. Survival (primary outcome), hemodynamics, and arterial blood gases including lactate were collected and analyzed up to 180 min after aortic rupture. RESULTS: The body temperature (mean ± standard deviation) in the hypothermic group was 31.5 ± 1.0 °C and 38.7 ± 0.4 °C in the normothermic group at the time for aortic rupture. Survival up to 180 min after the retroperitoneal bleeding was significantly higher in the hypothermic compared with the normothermic group (P = 0.023). CONCLUSIONS: Induced hypothermia did not impair survival in this experimental retroperitoneal aortic bleeding model in anesthetized pigs. This finding may indicate a minor role for the coagulation system in this type of bleeding.

The effect of an endovascular Heaney maneuver to achieve total hepatic isolation on survival, hemodynamic stability, retrohepatic bleeding, and collateral flow in a porcine model.

PURPOSE: Combining resuscitative endovascular balloon occlusion of the aorta (REBOA) and the inferior vena cava (REBOVC) with open surgery is a new hybrid approach for treating retrohepatic vena caval injuries. We compared endovascular total hepatic isolation with supraceliac REBOA ± suprahepatic REBOVC and no occlusion in experimental retrohepatic vena cava bleeding regarding survival, bleeding volume, hemodynamic stability, and arterial collateral blood flow. METHODS: Twenty-five anesthetized pigs (n = 6-7/group) were randomized to REBOA; REBOA + REBOVC; REBOA + infra and suprahepatic REBOVC + portal vein occlusion (endovascular Heaney maneuver, four-balloon-occlusion, 4BO) or no occlusion. After balloon inflation, free bleeding was initiated from an open sheath in the retrohepatic vena cava. Bleeding volume, right internal thoracic artery (RITA) blood flow, hemodynamics, and arterial blood variables were measured until death or up to 90 min. RESULTS: The REBOA group had a longer median survival time (63 min) compared with the 4BO (24 min, P = 0.02) and no occlusion (30 min, P = 0.02) groups, not versus the REBOA + REBOVC group (49 min, P > 0.05). The first 15 min accumulated bleeding was comparable in all groups (P > 0.05); Thereafter, bleeding volume was higher in the REBOA group versus the 4BO group (P < 0.05), not versus the other groups. RITA blood flow and MAP were higher in the REBOA group versus the other groups after 10 min of bleeding (P < 0.05). CONCLUSIONS: Endovascular Heaney maneuver was not beneficial for survival or hemodynamic stability in this porcine model, whereas supraceliac REBOA was. Anatomical differences in thoracoabdominal collaterals between pigs and humans must be considered when interpreting these results.

A porcine study of ultrasound-guided versus fluoroscopy-guided placement of endovascular balloons in the inferior vena cava (REBOVC) and the aorta (REBOA).

Objectives: In fluoroscopy-free settings, alternative safe and quick methods for placing resuscitative endovascular balloon occlusion of the aorta (REBOA) and resuscitative endovascular balloon occlusion of the inferior vena cava (REBOVC) are needed. Ultrasound is being increasingly used to guide the placement of REBOA in the absence of fluoroscopy. Our hypothesis was that ultrasound could be used to adequately visualize the suprahepatic vena cava and guide REBOVC positioning, without significant time-delay, when compared with fluoroscopic guidance, and compared with the corresponding REBOA placement. Methods: Nine anesthetized pigs were used to compare ultrasound-guided placement of supraceliac REBOA and suprahepatic REBOVC with corresponding fluoroscopic guidance, in terms of correct placement and speed. Accuracy was controlled by fluoroscopy. Four intervention groups: (1) fluoroscopy REBOA, (2) fluoroscopy REBOVC, (3) ultrasound REBOA and (4) ultrasound REBOVC. The aim was to carry out the four interventions in all animals. Randomization was performed to either fluoroscopic or ultrasound guidance being used first. The time required to position the balloons in the supraceliac aorta or in the suprahepatic inferior vena cava was recorded and compared between the four intervention groups. Results: Ultrasound-guided REBOA and REBOVC placement was completed in eight animals, respectively. All eight had correctly positioned REBOA and REBOVC on fluoroscopic verification. Fluoroscopy-guided REBOA placement was slightly faster (median 14 s, IQR 13-17 s) than ultrasound-guided REBOA (median 22 s, IQR 21-25 s, p=0.024). The corresponding comparisons of the REBOVC groups were not statistically significant, with fluoroscopy-guided REBOVC taking 19 s, median (IQR 11-22 s) and ultrasound-guided REBOVC taking 28 s, median (IQR 20-34 s, p=0.19). Conclusion: Ultrasound adequately and quickly guide the placement of supraceliac REBOA and suprahepatic REBOVC in a porcine laboratory model, however, safety issues must be considered before use in trauma patients. Level of evidence: Prospective, experimental, animal study. Basic science study.

A randomized porcine study of the hemodynamic and metabolic effects of combined endovascular occlusion of the vena cava and the aorta in normovolemia and in hemorrhagic shock.

BACKGROUND: Mortality from traumatic retrohepatic venous injuries is high and methods for temporary circulatory stabilization are needed. We investigated survival and hemodynamic and metabolic effects of resuscitative endovascular balloon occlusion of the aorta (REBOA) and vena cava inferior (REBOVC) in anesthetized pigs. METHODS: Twenty-five anesthetized pigs in normovolemia or severe hemorrhagic shock (controlled arterial bleeding in blood bags targeting systolic arterial pressure of 50 mm Hg, corresponding to 40-50% of the blood volume) were randomized to REBOA zone 1 or REBOA+REBOVC zone 1 (n = 6-7/group) for 45 minutes occlusion, followed by 3-hour resuscitation and reperfusion. Hemodynamic and metabolic variables and markers of end-organ damage were measured regularly. RESULTS: During occlusion, both the REBOA groups had higher systemic mean arterial pressure (MAP) and cardiac output (p < 0.05) compared with the two REBOA+REBOVC groups. After 60 minutes reperfusion, there were no statistically significant differences between the two REBOA groups and the two REBOA+REBOVC groups in MAP and cardiac output. The two REBOA+REBOVC groups had higher arterial lactate and potassium concentrations during reperfusion, compared with the two REBOA groups (p < 0.05). There was no major difference in end-organ damage markers between REBOA and REBOA+REBOVC. Survival after 1-hour reperfusion was 86% and 100%, respectively, in the normovolemic REBOA and REBOA+REBOVC groups, and 67% and 83%, respectively, in the corresponding hemorrhagic shock REBOA and REBOA+REBOVC groups. CONCLUSION: Acceptable hemodynamic stability during occlusion and short-term survival can be achieved by REBOA+REBOVC with adequate resuscitation; however, the more severe hemodynamic and metabolic impacts of REBOA+REBOVC compared with REBOA must be considered. LEVEL OF EVIDENCE: Prospective, randomized, experimental animal study. Basic science study, therapeutic.

Evaluation of Very Integrated Program: Health Promotion for Patients With Alcohol and Drug Addiction-A Randomized Trial.

BACKGROUND: Compared to the general population, patients with alcohol and drug addiction have an increased risk of additional hazardous lifestyles and suffer from more chronic diseases, adding to their already significantly higher morbidity and mortality. The objective of this study was to test the efficacy of the Very Integrated Program (VIP) on treatment and health outcomes for patients diagnosed with alcohol and drug addiction. METHODS: Parallel randomized clinical trial with intervention as add-on to addiction care as usual. A total of 322 patients aged 18 years or older were identified, and the study requirements were fulfilled by 219 patients, 7 of whom participated in a pilot. The intervention was a 6-week intensive, tailored, educational program that included motivational interviewing, a smoking cessation program, dietary and physical activity counseling, and patient education. The main outcome measures were substance-free days, time to relapse, and treatment adherence assessed after 6 weeks and 12 months. Secondary outcomes were lifestyle factors, symptoms of comorbidity, and quality of life. Missing data were imputed conservatively by using data closest to the follow-up date and baseline values in patients with no follow-up. RESULTS: The 212 patients (intervention, n = 113; control, n = 99) were randomized, and 202 had complete data for primary outcomes. After 6 weeks, there were no significant differences between the groups regarding primary or secondary outcomes. At the 12-month follow-up, the patients in the control group had significantly more total substance-free days (139 days; ranging 0 to 365 vs. 265; 0 to 366, p = 0.021)-specifically among the patients with drug addiction-and higher physical and mental quality of life (45 vs. 58, p = 0.049 and 54 vs. 66, p = 0.037), but not in the per-protocol analysis (60 vs. 46, p = 0.52 and 70 vs. 66, p = 0.74). The sensitivity analyses did not support significant differences between the groups. CONCLUSION: Overall, adding VIP intervention did not improve outcome of the alcohol or drug addiction care or the lifestyle compared to the addiction care alone. This patient group is still in need of effective programs, and new intervention research is required to develop that.

Resuscitative endovascular balloon occlusion of the inferior vena cava is made hemodynamically possible by concomitant endovascular balloon occlusion of the aorta-A porcine study.

BACKGROUND: Resuscitative endovascular balloon occlusion of the vena cava inferior (REBOVC) may provide a minimal invasive alternative for hepatic vascular and inferior vena cava isolation in severe retrohepatic bleeding. However, circulatory stability may be compromised by the obstruction of venous return. The aim was to explore which combinations of arterial and venous endovascular balloon occlusions, and the Pringle maneuver, are hemodynamically possible in a normovolemic pig model. The hypothesis was that lower-body venous blood pooling from REBOVC can be avoided by prior resuscitative endovascular aortic balloon occlusion (REBOA). METHODS: Nine anesthetized, ventilated, instrumented, and normovolemic pigs were used to explore the hemodynamic effects of 11 combinations of REBOA and REBOVC, with or without the Pringle maneuver, in randomized order. The occlusions were performed for 5 minutes but interrupted if systolic blood pressure dropped below 40 mm Hg. Hemodynamic variables were measured. RESULTS: Proximal REBOVC, isolated or in combination with other methods of occlusion, caused severely decreased systemic blood pressure and cardiac output, and had to be terminated before 5 minutes. The decreases in systemic blood pressure and cardiac output were avoided by REBOA at the same or a more proximal level. The Pringle maneuver had similar hemodynamic effects to proximal REBOVC. CONCLUSION: A combination of REBOA and REBOVC provides hemodynamic stability, in contrast to REBOVC alone or with the Pringle maneuver, and may be a possible adjunct in severe retrohepatic venous bleedings.

Compliance with the Very Integrated Program (VIP) for Smoking Cessation, Nutrition, Physical Activity and Comorbidity Education Among Patients in Treatment for Alcohol and Drug Addiction.

Meeting adherence is an important element of compliance in treatment programmes. It is influenced by several factors one being self-efficacy. We aimed to investigate the association between self-efficacy and meeting adherence and other factors of importance for adherence among patients with alcohol and drug addiction who were undergoing an intensive lifestyle intervention. The intervention consisted of a 6-week Very Integrated Programme. High meeting adherence was defined as >75% participation. The association between self-efficacy and meeting adherence were analysed. The qualitative analyses identified themes important for the patients and were performed as text condensation. High self-efficacy was associated with high meeting adherence (ρ = 0.24, p = 0.03). In the multivariate analyses two variables were significant: avoid complications (OR: 0.51, 95% CI: 0.29-0.90) and self-efficacy (OR: 1.28, 95% CI: 1.00-1.63). Reflections on lifestyle change resulted in the themes of Health and Wellbeing, Personal Economy, Acceptance of Change, and Emotions Related to Lifestyle Change. A higher level of self-efficacy was positively associated with meeting adherence. Patients score high on avoiding complications but then adherence to the intervention drops. There was no difference in the reflections on lifestyle change between the group with high adherence and the group with low adherence.

A cluster of deaths involving 5-(2-aminopropyl)indole (5-IT).

During 2012, the designer drug 5-(2-aminopropyl)indole emerged in Sweden, and became available at different web sites under the name 5-IT or 5-API. This compound is an indole derivative and a positional isomer of alpha-methyltryptamine. In this paper, we report the pathology and toxicology from 15 deaths involving 5-IT. Routine postmortem toxicology was performed in femoral blood, using a targeted screening for pharmaceuticals and drugs of abuse with liquid chromatography time-of-flight technology, and positive results were quantified using chromatographic techniques. For 5-IT, a new method was developed using ultra-high-performance liquid chromatography and tandem mass spectrometry. In 11 cases, intoxication was the cause of death. Two cases were signed out as causa ignota, and they were considered to be natural deaths. All determinations of 5-IT were performed in femoral blood and the concentrations ranged from 0.7 to 18.6 µg/g. Two cases had 5-IT as the only drug identified, while the others presented with other psychotropic drugs or medications in the blood as well. Shortly after this series of deaths, 5-IT was scheduled as a hazardous substance according to the regulation Certain Goods Dangerous to Health on 18 September 2012 prohibiting the handling and selling of the drug. Since then, no positive cases have been found.

An accidental fatal intoxication with methoxetamine.

This paper reports an unintentional death involving the administration of methoxetamine [2-(3-methoxyphenyl)-2-(ethylamino)-cyclohexanone] and offers some reference values from living drug abusers. Methoxetamine is a new recreational drug with a similar structure to ketamine. The deceased was a 26-year-old male with a history of drug abuse; he was found lying on the floor in his apartment. Several "red-line" plastic bags were found, one of which was labeled "2-(3-methoxyphenyl)-2-(ethylamino)-cyclohexanone" and another labeled "Haze." In four cases from living subjects with unknown doses, concentrations of methoxetamine were found from 0.13 to 0.49 µg/g. In three of the cases, the blood samples also contained natural or synthetic cannabinoids. In the autopsy case, a considerably higher concentration of methoxetamine, 8.6 µg/g, was found in femoral blood. In addition, tetrahydrocannabinol and the three different synthetic cannabinoids AM-694, AM-2201, and JWH-018, were present in femoral blood. The circumstances and the high femoral blood concentration of methoxetamine point toward an unintentional, acute fatal intoxication with methoxetamine, although the presence of the three synthetic cannabinoids may have contributed to the death.

Two fatal intoxications with the new designer drug methedrone (4-methoxymethcathinone).

We report two fatalities involving the new designer drug methedrone, 4-methoxymethylcathinone. Blood was extracted with ethyl acetate after the addition of sodium hydroxide followed by evaporation and derivatization with TFAA before gas chromatography-mass spectrometry analysis. Hair was decontaminated and cut into segments, and after overnight extraction with acetonitrile/methanol/20 mM ammonium formate buffer (pH 3) (10:10:80), samples were analyzed by liquid chromatography-tandem mass spectrometry. The first case was treated in hospital, and blood was collected for drug screening. The concentration of methedrone in antemortem blood was 13.2 µg/g and in postmortem femoral blood 8.4 µg/g. The second case presented with 9.6 µg methedrone/g femoral blood, and in a hair sample, methedrone was detected in five short segments suggesting exposure to the drug during the months prior to death. In living abusers, the blood concentration range was 0.2-4.8 µg/g (n = 11). We conclude that use of methedrone may result in accidental death owing to its toxic properties and that the blood concentrations found in the two cases are close to those seen in the living. This suggests a rather narrow "therapeutic" window and emphasizes the danger in taking this kind of drug for recreational purposes.

Pycnanthuquinone C, an unusual 6,6,5-tricyclic Geranyltoluquinone from the Western Australian brown alga Cystophora harveyi.

Chemical investigation of the Western Australian marine brown alga Cystophora harveyi resulted in the isolation of the new linearly fused 6,6,5-tricyclic compound pycnanthuquinone C (1), in addition to four previously reported geranyltoluquinol derivatives. Structures were elucidated by interpretation of spectrometric data. Compounds with the same cyclic skeleton as 1 have been reported to be useful drug leads for the treatment of type 2 diabetes, while compounds 4 and 7 are known constituents of Chinese medicinal herbs. A biosynthetic scheme encompassing all of the geranyltoluquinol derivatives isolated from C. harveyi is proposed.

A2 (N-benzylpiperazine) a new drug of abuse in Sweden.

N-Benzylpiperazine was tested in the beginning of the 1970s as a possible antidepressant drug. However, in both animal and human studies, it was shown to possess amphetamine-like properties, and any further studies were stopped. In a forensic autopsy case in 1999, we found a substance so far unknown to us in the chromatogram of our method used for amphetamines. We could swiftly identify this compound as N-benzylpiperazine because of information given to us by a newly formed network comprising, among others, customs and the police. Since then, we have found N-benzylpiperazine in several cases, among them 11 cases from a number of prisons.