Vasopressin impairs brain, heart and kidney perfusion: an experimental study in pigs after transient myocardial ischemia

Introduction: Arginine vasopressin (AVP) is increasingly used to restore mean arterial pressure (MAP) in low-pressure shock states unresponsive to conventional inotropes. This is potentially deleterious since AVP is also known to reduce cardiac output by increasing vascular resistance. The effects of AVP on blood flow to vital organs and cardiac performance in a circulation altered by cardiac ischemia are still not sufficiently clarified. We hypothesised that restoring MAP by low dose, therapeutic level AVP would reduce vital organ blood flow in a setting of experimental acute left ventricular dysfunction. Methods: Cardiac output (CO) and arterial blood flow to the brain, heart, kidney and liver were measured in nine pigs using transit-time flow probes. Left ventricular pressure-volume catheter and central arterial and venous catheters were used for haemodynamic recordings and blood sampling. Transient left ventricular ischemia was induced by intermittent left coronary occlusions resulting in a 17% reduction in cardiac output and a drop in MAP from 87 ± 3 to 67 ± 4 mmHg (p < 0.001). A low-dose therapeutic level of AVP (0.005 U/kg/min) was used to restore MAP to pre-ischemic values (93 ± 4 mmHg). Results: AVP further impaired systemic perfusion (CO and brain, heart and kidney blood flow reduced by 29, 18, 23 and 34%, respectively) due to a 2.0-, 2.2-, 1.9- and 2.1-fold increase in systemic, brain, heart and kidney specific vascular resistances. The hypoperfusion induced by AVP was associated with an increased systemic oxygen extraction. Oxygen saturation in blood drawn from the great cardiac vein fell from 29 ± 1 to 21 ± 3% (p = 0.01). Finally, these effects were reversed 40 min after AVP was withdrawn. Conclusion: Low dose AVP induced a pronounced reduction in vital organ blood flow in pigs after transient cardiac ischemia. This indicates a potentially deleterious effect of AVP in patients with heart failure or cardiogenic shock due to impaired coronary perfusion

Cooling to hypothermic circulatory arrest by immersion vs. cardiopulmonary bypass (CPB): Worse outcome after rewarming in immersion cooled pigs

Introduction: Cooling by cardiopulmonary bypass (CPB) to deep hypothermic cardiac arrest (HCA) for cardiac surgical interventions, followed by CPB-rewarming is performed on a routine basis with relatively low mortality. In contrast, victims of deep accidental hypothermia rewarmed with CPB generally have a much worse prognosis. Thus, we have developed an intact pig model to compare effects on perfusion pressures and global oxygen delivery (DO2) during immersion cooling versus cooling by CPB. Further, we compared the effects of CPB-rewarming between groups, to restitute cardiovascular function, brain blood flow, and brain metabolism. Materials and Methods: Total sixteen healthy, anesthetized juvenile (2–3 months) castrated male pigs were randomized in a prospective, open placebo-controlled experimental study to immersion cooling (IMMc, n = 8), or cooling by CPB (CPBc, n = 8). After 75 minutes of deep HCA in both groups, pigs were rewarmed by CPB. After weaning from CPB surviving animals were observed for 2 h before euthanasia. Results: Survival rates at 2 h after completed rewarming were 4 out of 8 in the IMMc group, and 8 out of 8 in the CPBc group. Compared with the CPBc-group, IMMc animals showed significant reduction in DO2, mean arterial pressure (MAP), cerebral perfusion pressure, and blood flow during cooling below 25◦C as well as after weaning from CPB after rewarming. After rewarming, brain blood flow returned to control in CPBc animals only, and brain micro dialysate-data showed a significantly increase in the lactate/pyruvate ratio in IMMc vs. CPBc animals Conclusion: Our data indicate that, although global O2 consumption was independent of DO2, regional ischemic damage may have taken place during cooling in the brain of IMMc animals below 25◦C. The need for prolonged extracorporeal membrane oxygenation (ECMO) should be considered in all victims of accidental hypothermic arrest that cannot be weaned from CPB immediately after rewarming

Acute heart failure syndromes : treatment, outcomes and pathophysiological aspects of inflammation and vascular function

Akutt hjertesvikt, spesielt ved sirkulatorisk kollaps, er en dramatisk tilstand med høy dødelighet. Forekomsten av akutt hjertesvikt er økende og tilgjengelig kunnskap om sykdomsmekanismene samt medisinsk behandling er begrenset.De siste tiår har det vært en revolusjonerende utvikling i behandlingen av og overlevelsen ved iskemisk hjertesykdom og akutt hjerteinfarkt. Tilsvarende utvikling har det dessverre ikke vært i behandlingen av akutt hjertesvikt som er et økende problem assosiert med høy dødelighet. Formålet med dette prosjektet har vært å kartlegge epidemiologi, behandling og prognose ved forskjellige typer akutt hjertesvikt. For å øke den patofysiologiske forståelsen av sirkulasjonsregulering ved de mest alvorlige former for akutt hjertesvikt (kardiogent sjokk) har vi gjennomført observajonsstudier av biokjemiske responser og perifer karfunksjon i sykdomsforløpet. Prosjektet har vært todelt. Vi har først har sett på forekomsten av forskjellige typer akutt hjertesvikt og behandlingen som ble gitt ved medisinsk og kirurgisk intensiv avdeling ved UNN over en 2 års periode. Tross moderne behandling med bla tidlig revaskularisering døde ca 1/4 av pasientene under sykehusoppholdet. Dårligst prognose hadde de med kardiogent sjokk der nesten halvparten døde. De med lettere former for akutt hjertesvikt hadde meget dårlige leveutsikter i perioden etter utskrivelse og kun 50 % var i live etter to år. Mer utstrakt og tidlig bruk av mekanisk sirkulasjonsstøtte (hjertepumper) kan potensielt bedre overlevelsen hos de med mest alvorlig og behandlingsrefraktær hjertesvikt. Hos pasienter med kardiogent sjokk og alvorlig hjertesvikt etter hjertekirurgi er dårlig respons på konvensjonelle blodtrykksøkende medikamenter forbundet med spesielt dårlig prognose. For å kartlegge de underliggende mekanismene ved sirkulasjonssvikt spesielt mtp perifer sirkulasjonsregulering har vi målt perifer karfunksjon (endotelfunksjon), markører på systemisk inflammasjon og sirkulerende NO-blokkere (ADMA) under sykdomsforløpet. Tilstanden var karakterisert av en betydelig systemisk inflammasjon samt redusert perifer karfunksjon. Høye nivå av ADMA var assosiert med organsvikt og graden av hypoperfusjon

Inflammation and reduced endothelial function in the course of severe acute heart failure

Systemic inflammation and elevated circulating levels of the endogenous nitric oxide inhibitor asymmetrical dimethylarginine (ADMA) have been associated with increased risk in cardiogenic shock (CS). In this prospective study, we assessed, over 4 consecutive days, the changes and possible associations between vascular function, markers of inflammation, and circulating ADMA levels in patients with CS (n = 12) and postcardiotomy heart failure (n = 12, PC-HF). Vasodilator function was measured as a reactive hyperemia index (RH-index) using a finger plethysmograph. Blood samples were analyzed for plasma ADMA, interleukine-6, interleukine-8, intracellular adhesion molecule-1, and vascular adhesion molecule-1. Baseline RH-index was significantly attenuated compared with healthy controls (2.28) for both CS and PC-HF (1.35 and 1.45, respectively, P = 0.001). Although vasodilator function improved in PC-HF patients, it remained attenuated in CS. Inflammatory markers were markedly elevated followed by a significant fall during the observation period in both groups. ADMA levels increased significantly during the observation period for PC-HF, whereas no pattern of change was observed for CS. No association was found between the longitudinal changes in RH-index, markers of inflammation, or ADMA in CS. However, an improved RH-index was associated with decreasing inflammatory markers in PC-HF. ADMA correlated to arterial lactate levels and the degree of organ dysfunction in CS. In conclusion, CS and PC-HF were characterized by a marked inflammatory activation accompanied by an attenuated vasodilator function. ADMA was related to organ dysfunction and degree of hypoperfusion during CS but showed no correlations to inflammation or hampered vasodilator function. The pathogenic significance of these responses needs clarificatio

Clinical guided computer tomography decisions are advocated in potentially severely injured trauma patients: a one-year audit in a level 1 trauma centre with long pre-hospital times

Background - The International Commission on Radiological Protection’s (ICRP) justification principles state that an examination is justified if the potential benefit outweighs the risk for radiation harm. Computer tomography (CT) contributes 50% of the radiation dose from medical imaging, and in trauma patients, the use of standardized whole body CT (SWBCT) increases. Guidelines are lacking, and reviews conclude conflictingly regarding the benefit. We aimed to study the degree of adherence to ICRP’s level three justification, the individual dose limitation principle, in our institution. Methods - This is a retrospective clinical audit. We included all 144 patients admitted with trauma team activation to our regional Level 1 trauma centre in 2015. Injuries were categorized according to the Abbreviated Injury Scale (AIS) codes. Time variables, vital parameters and interventions were registered. We categorized patients into trauma admission SWBCT, selective CT or no CT examination strategy groups. We used descriptive statistics and regression analysis of predictors for CT examination strategy. Results - The 144 patients (114 (79.2%) males) had a median age of 31 (range 0–91) years. 105 (72.9%) had at least one AIS ≥ 2 injury, 26 (18.1%) in more than two body regions. During trauma admission, at least one vital parameter was abnormal in 46 (32.4%) patients, and 73 (50.7%) underwent SWBCT, 43 (29.9%) selective CT and 28 (19.4%) no CT examination. No or only minor injuries were identified in 17 (23.3%) in the SWBCT group. Two (4.6%) in the selective group were examined with a complement CT, with no new injuries identified. A significantly (p 0.001) lower proportion of children (61.5%) than adults (89.8%) underwent CT examination despite similar injury grades and use of interventions. In adjusted regression analysis, patients with a high-energy trauma mechanism had significantly (p = 0.028) increased odds (odds ratio = 4.390, 95% confidence interval 1.174–16.413) for undergoing a SWBCT. Conclusion - The high proportion of patients with no or only minor injuries detected in the SWBCT group and the significantly lower use of CT among children, indicate that use of a selective CT examination strategy in a higher proportion of our patients would have approximated the ICRP’s justification level three, the individual dose limitation principle, better

Health-related quality of life after extracorporeal membrane oxygenation: a single centre's experience

Aims: The aims of this study were to evaluate health-related quality of life (HRQL) among patients treated with extracorpo-real membrane oxygenation (ECMO) in northern Norway over a period of 27years (1988–2015) and to identify variables related to HRQL. Methods and results: A retrospective inquiry of the ECMO registry at the University Hospital of North Norway identified 74 ECMO-treated patients (mean age 49 years, 65% males). Acute cardiac failure was the dominant indication (58%), and venoarterial ECMO was the dominant mode of treatment (87%). Mortality for discharged patients was recorded on 20 September 2016. Thirty (41%) survivors were identified. Twenty-three survivors were eligible for the survey and received a set of questionnaires at home. The main outcome measure was HRQL as measured with the 36-item Short-Form health survey (SF-36) (RAND Short Form-36 v1.2). Other questionnaires covered demographic information, problems with functioning in usual daily activities (such as hobbies, household chores, family, or work), employment status, and psychological distress. The survey was completed by 20 (87%) survivors (mean age =49 years, 12 men). Indications for ECMO treatment (VA = 90%) had been respiratory failure (25%), cardiac failure (60%), and extracorporeal cardiopulmonary resuscitation (15%). The average time since ECMO treatment was 6.5 years. Seventy-five percent reported mental HRQL (SF-36 Mental Component Summary,mean =43,SD=5) or physical HRQL (SF-36 Physical Component Summary, mean =43,SD=4.5) within the normal range(T=50±10) in comparison with age-matched population data from national norms. Half of the responders reported problems on the SF-36 subscales general health and role physical. Seventy percent reported problems on the SF-36 subscale role emotional. All but one responder lived independently without any organized care, and 90% reported no problems related to basic self-care. Half of those in working age had returned to work after ECMO treatment. Forty percent of the responders reported some degree of restrictions in usual daily activities, problems with mobility (35%), anxiety/depression (35%), or pain/discomfort (55%). Significant univariate associations were observed for poorer HRQL and higher reports of psychological distress, pain, and experiencing restrictions in usual everyday activities. Improved HRQL was significantly related to an extended time since ECMO treatment. Conclusions: Our survey indicates an overall positive long-term HRQL outcome for our ECMO survivors. A subset reported problems with functioning and HRQL. Future research should focus on identification of the survivors at risk for poor recovery who may benefit from rehabilitation interventions

Direct angiography demonstrates equal 8-12 years patency rates of radial artery and saphenous vein grafts

Objectives: The benefits of coronary artery bypass surgery depend on lasting graft patency. To aid rational graft selection, the relative long-term merits of radial artery and saphenous vein grafts need to be determined by a gold standard method and with minimal clinically driven selection bias. Methods: The patency rates of various conduits were determined by direct angiography in 76 patients from a cohort of 119 undergoing coronary artery bypass grafting 7.6–12.1 (mean 8.9) years before. Results: 14 out of 76 radial artery and 10 out of 61 saphenous vein grafts were occluded (rates 0.18 and 0.16, respectively). Conclusion: The high long-term patency rate of saphenous vein grafts does not support a preferential use of the radial artery as a coronary artery bypass conduit