Kristofer F. Nilsson

A case of partial aortic balloon occlusion in an unstable multi-trauma patient

The usage of aortic balloon occlusion or resuscitative endovascular balloon occlusion of the aorta in trauma management for bleeding control is increasing rapidly as an alternative to thoracotomy and aortic clamping. Little is known about the effects of partial occlusion of the aorta as a bridge to definitive treatment, but one of its advantages may be limited visceral organ ischemia. We describe the first known case of partial aortic balloon occlusion in trauma for reaching a targeted systolic blood pressure, which was used as an adjunctive tool in trauma management and as a bridge to definitive treatment.

Release and inhibitory effects of prostaglandin D2 in guinea pig urinary bladder and the role of urothelium

BACKGROUND While studying a urothelium-derived inhibitory factor in guinea pig urinary bladders we observed considerable release of prostanoids, including PGD2-like activity. The present study was carried out to identify the prostanoids and to study their roles in modulating guinea pig urinary bladder motility. METHODS Release of PGE2 and PGD2 in isolated guinea pig urinary bladder preparations was analyzed by high performance liquid chromatography (HPLC) combined with bioassay on bladder strips. Isolated urothelium-intact (UI) or -denuded (UD) bladder strips were subjected to electrical field stimulation (EFS) and applications of PGE2 and PGD2. RESULTS A resting release of 95±9 (n=5) nggtissue(-1)h(-1) PGE2-like activity and 210±34 (n=4) nggtissue(-1)h(-1) PGD2-like activity was found, where PGD2-like was subject to marked spontaneous inactivation during isolation. Prostanoids release was decreased by 70-90% by the cyclo-oxygenase inhibitor diclofenac in UI preparations. Urothelium removal decreased prostanoids release by more than 90%. PGE2 increased basal tone and spontaneous contractions, whereas PGD2 had little or no effect on these. Exogenous PGE2 enhanced and PGD2 inhibited contractile responses to EFS, exogenous acetylcholine- and ATP, whereas PGD2 caused marked dose-dependent inhibition. PGE2 and PGD2 effects were more pronounced in diclofenac-treated UD tissues. CONCLUSIONS PGD2 and PGE2 are released from guinea pig bladder urothelium and PGD2 has inhibitory effects on bladder motility, mainly through a postjunctional action on smooth muscle responsiveness. GENERAL SIGNIFICANCE The release and inhibitory effects merit further studies in relation to normal biological function as well as overactive bladder syndrome.

Formation of new bioactive organic nitrites and their identification with gas chromatography-mass spectrometry and liquid chromatography coupled to nitrite reduction.

Nitric oxide (NO) donors, notably organic nitrates and nitrites are used therapeutically but tolerance develops rapidly, making the use of e.g. nitroglycerin difficult. NO donation in the pulmonary vascular bed might be useful in critically ill patients. Organic nitrites are not associated with tachyphylaxis but may induce methaemoglobinemia and systemic hypotension which might hamper their use. We hypothesised that new lung-selective NO donors can be identified by utilizing exhaled NO as measure for pulmonary NO donation and systemic arterial pressure to monitor hypotension and tolerance development. Solutions of alcohols and carbohydrates were reacted with NO gas and administered to ventilated rabbits for evaluation of in vivo NO donation. Chemical characterization was made by liquid chromatography with on-line nitrite reduction (LC-NO) and by gas chromatography-mass spectrometry (GC-MS). In vivo experiments showed that the hydroxyl-containing compounds treated with NO gas yielded potent NO donors, via nitrosylation to organic nitrites. Analyses by LC-NO showed that the reaction products were able to release NO in vitro. In GC-MS the reaction products were determined to be the organic nitrites, where some are new chemical entities. Non-polar donors preferentially increased exhaled NO with less effect on systemic blood pressure whereas more polar molecules had larger effects on systemic blood pressure and less on exhaled NO. We conclude that new organic nitrites suitable for intravenous administration are produced by reacting NO gas and certain hydroxyl-containing compounds in aqueous solutions. Selectivity of different organic nitrites towards the pulmonary and systemic circulation, respectively, may be determined by molecular polarity.

Estimation of endogenous adenosine activity at adenosine receptors in guinea-pig ileum using a new pharmacological method.

Aim:  Adenosine modulates neurotransmission and in the intestine adenosine is continuously released both from nerves and from smooth muscle. The main effect is modulation of contractile activity by inhibition of neurotransmitter release and by direct smooth muscle relaxation. Estimation of adenosine concentration at the receptors is difficult due to metabolic inactivation. We hypothesized that endogenous adenosine concentrations can be calculated by using adenosine receptor antagonist and agonist and dose ratio (DR) equations.

Increase in exhaled nitric oxide and protective role of the nitric oxide system in experimental pulmonary embolism

Pulmonary embolism (PE) represents a real diagnostic challenge. PE is associated with pulmonary hypertension due to pulmonary vascular obstruction and vasoconstriction. We recently reported that pulmonary gas embolism transiently increases exhaled nitric oxide (FENO), but it is not known whether solid emboli may alter FENO, and whether an intact endogenous NO synthesis has a beneficial effect in experimental solid pulmonary embolism.

No-touch technique for radiocephalic arteriovenous fistula - surgical technique and preliminary results

Purpose The radiocephalic arteriovenous fistula (RC-AVF) has significant failure rates due to occlusions and failure to mature. The size and quality of the veins are considerable limiting factors for the procedure. The aim of this pilot study was to describe the No-Touch technique (NTT) to create RC-AVF and present the results up to 1 year of follow-up. Methods Thirty-one consecutive patients who were referred for surgery for a RC-AVF were included (17 men, mean age 63 years, range 35-84) and operated by NTT where the vein and artery were dissected with a tissue cushion around it. Twenty-two patients had small veins or arteries (≤2 mm), 12 patients had a small cephalic vein (≤2 mm), and the mean distal cephalic vein diameter was 2.4 mm (range 1.0-4.1 mm). Results Technical surgical success and immediate patency were obtained in all patients. Clinical success was achieved in 23 of the 27 (85%) patients who required hemodialysis. The proportion of primary patency at 30 days and 6 months was 84% and 64%, respectively. Secondary patency at 30 days and 6 months was 97% and 83%, respectively. At 1-year follow-up, primary patency was 54% and secondary patency was 80%. There was no major difference in patency due to preoperative vein diameter. Conclusions The results of this study indicate that NTT can be used for primary radio-cephalic fistula surgery with very good results. This method offers the potential to create a RC-AVF in patients who are not usually considered appropriate for a distal arm fistula due to a small cephalic vein.

Intra-abdominal Hypertension—An Experimental Study of Early Effects on Intra-abdominal Metabolism

BACKGROUND The main aim of this experimental study was to investigate the early effects of intra-abdominal hypertension (IAH) on intra-abdominal metabolism and intestinal mucosal blood flow to evaluate whether metabolites can serve as markers for organ dysfunction during IAH. METHODS A swine model was used, and the animals were anesthetized and ventilated. Fifteen animals were subjected to IAH of 30 mm Hg for 4 hr by carbon dioxide insufflation. Seven animals served as controls. Hemodynamic data, arterial blood samples, and urine output were analyzed. Intraluminal laser Doppler flowmetry measured intestinal mucosal blood flow. Glucose, glycerol, lactate, and pyruvate concentrations and lactate-to-pyruvate (l/p) ratio were measured intraperitoneally and intramurally in the small intestine and rectum using microdialysis. RESULTS IAH lowered the abdominal perfusion pressure by 12-18 mm Hg, reduced the intestinal mucosal blood flow by 45-63%, and decreased urine output by 50-80%. In the intervention group, glycerol concentrations increased at all locations, pyruvate concentrations decreased, and the l/p ratio increased intraperitoneally and intramurally in the small intestine. Control animals remained metabolically stable. Glucose and lactate concentrations were only slightly affected or unchanged in both the groups. CONCLUSIONS IAH reduces intestinal blood flow and urinary output and causes early metabolic changes, indicating a discrete shift toward anaerobic metabolism. Intraperitoneal microdialysis may be useful in the early detection of impaired organ dysfunction with metabolic consequences in IAH and abdominal compartment syndrome.

Blood pressure targeting by partial REBOA is possible in severe hemorrhagic shock in pigs and produces less circulatory, metabolic and inflammatory sequelae than total REBOA

BACKGROUND Resuscitative endovascular balloon occlusion of the aorta (REBOA) is an effective adjunct in exsanguinating torso hemorrhage, but causes ischemic injury to distal organs. The aim was to investigate whether blood pressure targeting by partial REBOA (pREBOA) is possible in porcine severe hemorrhagic shock and to compare pREBOA and total REBOA (tREBOA) regarding hemodynamic, metabolic and inflammatory effects. METHODS Eighteen anesthetized pigs were exposed to induced controlled hemorrhage to a systolic blood pressure (SBP) of 50 mmHg and randomized into three groups of thoracic REBOA: 30 min of pREBOA (target SBP 80-100 mmHg), tREBOA, and control. They were then resuscitated by autologous transfusion and monitored for 3 h. Hemodynamics, blood gases, mesenteric blood flow, intraperitoneal metabolites, organ damage markers, histopathology from the small bowel, and inflammatory markers were analyzed. RESULTS Severe hemorrhagic shock was induced in all groups. In pREBOA the targeted blood pressure was reached. The mesenteric blood flow was sustained in pREBOA, while it was completely obstructed in tREBOA. Arterial pH was lower, and lactate and troponin levels were significantly higher in tREBOA than in pREBOA and controls during the reperfusion period. Intraperitoneal metabolites, the cytokine response and histological analyses from the small bowel were most affected in the tREBOA compared to the pREBOA and control groups. CONCLUSION Partial REBOA allows blood pressure titration while maintaining perfusion to distal organs, and reduces the ischemic burden in a state of severe hemorrhagic shock. Partial REBOA may lower the risks of post-resuscitation metabolic and inflammatory impacts, and organ dysfunction.

Organic mononitrites of 1,2-propanediol act as an effective NO-releasing vasodilator in pulmonary hypertension and exhibit no cross-tolerance with nitroglycerin in anesthetized pigs

Purpose Clinically available intravenous (IV) nitric oxide (NO) donor drugs such as nitroglycerin (GTN) cause systemic hypotension and/or tolerance development. In a porcine model, novel NO donor compounds – the organic mononitrites of 1,2-propanediol (PDNO) – were compared to GTN with regard to pulmonary selectivity and tolerance development. The vasodilatory effects of inorganic nitrite were investigated. Materials and methods In anesthetized piglets, central hemodynamics were monitored. At normal pulmonary vascular resistance (PVR), IV infusions of PDNO (15–60 nmol kg−1 min−1), GTN (13–132 nmol kg−1 min−1), and inorganic nitrite (dosed as PDNO) were administered. At increased PVR (by U46619 IV), IV infusions of PDNO (60–240 nmol kg−1 min−1) and GTN (75–300 nmol kg−1 min−1) before and after a 5 h infusion of GTN (45 nmol kg−1 min−1) were given. Results At normal PVR, PDNO (n=12) and GTN (n=7) caused significant dose-dependent decreases in mean systemic and pulmonary arterial pressures, whereas inorganic nitrite (n=13) had no significant effect. At increased PVR, PDNO (n=6) and GTN (n=6) significantly decreased mean systemic and pulmonary pressures and resistances, but only PDNO reduced the ratio between pulmonary and systemic vascular resistances significantly. After the 5 h GTN infusion, the hemodynamic response to GTN infusions (n=6) was significantly suppressed, whereas PDNO (n=6) produced similar hemodynamic effects to those observed before the GTN infusion. Conclusion PDNO is a vasodilator with selectivity for pulmonary circulation exhibiting no cross-tolerance to GTN, but GTN causes non selective vasodilatation with substantial tolerance development in the pulmonary and systemic circulations. Inorganic nitrite has no vasodilatory properties at relevant doses.

Assessment of acute gastrointestinal injury score in postoperative cardiac surgical patients

Background: Postoperative complications increase the risk of death 2–3 years postoperatively. Prediction of complications can support clinical decisions. Before clinical use of any prediction model, validation is reasonable. We aimed to validatethree models: Revised Cardiac Risk Index (RCRI), ARISCAT and POSSUM.Methods: The PROF S-study was performed in four Swedish university hospitals. Patients werere cruited between 2015-11-01 and 2016-02-15. Inclusion criteria were adults, ASA classification ≥3, major/complex upper and lower gastrointestinal, urogenital or orthopedic surgery. Complications were screened on days 3, 7 and 10 by the postoperative morbidity survey (POMS). Only patients with grade≥2 (Clavien-Dindo classification) were accounted for. Study outcomes were cardiovascular (RCRI model) and pulmonary (ARISCAT model) complications, and a composite of the POMS domains (POSSUM model). Discrimination was evaluated by C-statistics (area under receiver operator characteristic curve; AUC ROC).Results: The number of patients included was 1089. Thirteen patients were excluded due to wrong inclusion, and another three were lost to follow-up. Presen ce of malignancy was 41%. Patient characteristics and outcomes are displayed in Table 1. The RCRI underestimated the risk for cardiovascular complications, and discrimination was low (AUC ROC 0.64; 95% CI 0.59–0.68). The prediction by the ARISCAT model was fair (AUC 0.72; CI 0.69–0.76). The POSSUM model had poor /fair discrimination (AUC 0.70; CI 0.67–0.73).Conclusions: The ARISCAT model predicted pulmonary complications with fair discrimina-tion and so could be used as decision support. Parameters with significant odds ratios of the RCRI and POSSU M models might be used as complements of clinical judgement.Background: In elderly reclassification of ASA3 class by functional dependency improved prediction of postoperative mortality. We hypothesized that such a reclassification could improve the risk pred ...