Extracorporeal cardiopulmonary resuscitation after out-of-hospital cardiac arrest in a Danish health region.

BACKGROUND: Extracorporeal Cardiopulmonary Resuscitation (ECPR) has emerged as a feasible rescue therapy for refractory, normothermic out-of-hospital cardiac arrest (OHCA). Reported survival rates vary and comparison between studies is hampered by heterogeneous study populations, differences in bystander intervention and in pre-hospital emergency service organisation. We aimed to describe the first experiences, treatment details, complications and outcome with ECPR for OHCA in a Danish health region. METHODS: Retrospective study of adult patients admitted at Aarhus University Hospital, Denmark between 1 January 2011 and 1 July 2015 with witnessed, refractory, normothermic OHCA treated with ECPR. OHCA was managed with pre-hospital advanced airway management and mechanical chest compression during transport. Relevant pre-hospital and in-hospital data were collected with special focus on low-flow time and ECPR duration. Survival to hospital discharge with Cerebral Performance Category (CPC) of 1 and 2 at hospital discharge was the primary endpoint. RESULTS: Twenty-one patients were included. Median pre-hospital low-flow time was 54 min [range 5-100] and median total low-flow time was 121 min [range 55-192]. Seven patients survived (33%). Survivors had a CPC score of 1 or 2 at hospital discharge. Five survivors had a shockable initial rhythm. In all survivors coronary occlusion was the presumed cause of cardiac arrest. CONCLUSION: Extracorporeal cardiopulmonary resuscitation is feasible as a rescue therapy in normothermic refractory OHCA in highly selected patients. Low-flow time was longer than previously reported. Survival with favourable neurological outcome is possible despite prolonged low-flow duration.

High thoracic epidural analgesia decreases stress hyperglycemia and insulin need in cardiac surgery patients.

OBJECTIVE: Assuming that high thoracic epidural analgesia (HTEA) with the sympathetic block might decrease postoperative blood glucose (BG) level and reduce the need of insulin, the aim was to evaluate the effect of HTEA on the BG level and insulin requirement in patients undergoing cardiac surgery. MATERIALS AND METHODS: Forty-two low-risk patients age 65-79 years scheduled for elective coronary artery bypass grafting with or without aortic valve replacement were randomised to receive HTEA as supplement for general anaesthesia. BG and lactate were measured before and after cardiopulmonary bypass and postoperatively at least every 3 h together with administration of insulin. Postoperative pain was evaluated 30 min, 2, 4 and 6 h after extubation, and before discharge from the intensive care unit. RESULTS: Overall BG levels showed great variation over time (P < 0.001). No statistically significant difference was found in perioperative BG, but postoperative lower BG levels were found in HTEA patients (P = 0.042). The number of patients not receiving insulin in postoperative period was significantly higher in HTEA group (9 vs. 2, P = 0.032). No differences were seen in lactate levels. Patients in the HTEA group had significant lower pain scores (P < 0.001). CONCLUSION: HTEA preserves glucose metabolism better and leads to a lesser degree of 'stress hyperglycaemia' in cardiac surgery patients.

Sufentanil preserves hemodynamics and left ventricular function in patients with ischemic heart disease.

OBJECTIVE: Sufentanil has been reported to provide stable hemodynamics similar to other opioids. However, it has not been reliably established whether this stability can be attributed only to Sufentanil and translates into fully preserved left ventricular (LV) function. The purpose of this study was to evaluate the effect of Sufentanil on hemodynamics and LV systolic and diastolic function using invasive monitoring and echocardiography in patients with ischemic heart disease. METHODS: Prospective observational study of thirty patients acting as their own control undergoing echocardiographic imaging before and after bolus Sufentanil 1.5-2.0 µg/kg. Full invasive hemodynamic monitoring was established before Sufentanil administration. Global LV systolic function was evaluated with a global longitudinal peak systolic strain (GLPSS) by speckle tracking ultrasound; systolic displacement by tissue tracking (TT) and diastolic function was evaluated using Doppler tissue imaging and pulse wave Doppler. RESULTS: Hemodynamic monitoring showed a minor decline in systolic blood pressure from 159 to 154 mmHg (P=0.046). No changes were observed in the cardiac index, stroke volume index and heart rate. An unchanged TT score index (9.9 vs. 10.2 mm, P=0.428) and GLPSS (14.3 vs. 14.5%, P=0.658) indicated preserved LV global systolic function and unchanged E'/A' (0.95 vs. 0.89, P=0.110) and E/E' ratio (15.4 vs. 14.9, P=0.612) indicated unchanged diastolic function. CONCLUSION: Sufentanil preserves hemodynamic parameters as well as echocardiographic indices of LV systolic and diastolic function in patients with ischemic heart disease (IHD).

Growth hormone and insulin-like growth factor-I counteracts established steroid catabolism in rats by effects on hepatic amino-N degradation.

BACKGROUND/AIMS: Long-term steroid treatment causes protein wasting. Liver contributes towards this by upregulating ureagenesis. Growth hormone (GH) and insulin-like growth factor-I (IGF-I) are anabolic agents with specific hepatic effects. It is unknown whether IGF-I alone and/or in combination with GH have any effect on established hepatic amino-N catabolism during long-term glucocorticoid treatment. METHODS: We measured the spontaneous (UNSR) and the substrate standardized rate of urea nitrogen synthesis (STUNSR), N-balance and mRNA levels of urea cycle enzymes in controls (placebo) and four longterm steroid treated groups given (1) prednisolone 4 mg/kg/day during 28 days (St) (2) +GH 1 mg/kg/day from day 21-28 (StGH) (3) +IGF-I 1.5 mg/kg/day 21-28 (StIGF) (4) GH +IGF-I (StGHIGF). RESULTS: Steroid induced weight loss was stepwisely reversed by IGF-I, GH and both. UNSR, STUNSR and mRNA levels of urea cycle enzymes in the liver increased markedly after steroid treatment, and was normalized after co-administration of GH and IGF-I. N-balance improved after GH and IGF-I administration. CONCLUSIONS: Our results expands the knowledge of beneficial effects of GH on short-term steroid catabolism to include effects of IGF-I and IGF-I combined with GH on long-term steroid catabolism. Both peptides prevent steroid induced hepatic protein wasting and thereby contribute towards whole body anabolism. The effect in vivo is probably due to an effect of the peptides on urea cycle enzyme mRNA.

Acute effects of moderate dehydration on the hepatic conversion of amino nitrogen into urea nitrogen in healthy men.

Intracellular hydration may play a role in the regulation of protein and nitrogen metabolism. The hepatic removal of nitrogen by urea synthesis has a key regulatory role in nitrogen balance. The purpose of the present study was to establish the acute effects of dehydration on the hepatic kinetics of urea synthesis, quantified by functional hepatic nitrogen clearance (FHNC), in healthy volunteers. Seven healthy men were studied twice in random order. On both study days, a primed continuous infusion of alanine was given. On the day of dehydration an intravenous bolus injection of a loop diuretic (furosemide, 1 mg/kg) was superimposed. FHNC was calculated as the ratio between measured synthesis rates of urea nitrogen and blood alanine concentrations. Furosemide induced a weight loss of 1 kg. During dehydration, FHNC decreased by approx. 25% (41+/-11 to 54+/-10 litres/h; P<0.02). On both occasions individual FHNC and glucagon values were positively correlated (r(2)>0.6). In addition, dehydration more than halved the linear slope of the relationship (P<0.05). The FHNC values were correlated with the urinary excretion of both potassium and sodium (r(2)=0.68, P<0.01 and r(2)=0.62, P<0.02 respectively). Changes in the reactivity of urea synthesis to glucagon (i.e. the ratio between FHNC and glucagon concentration) was negatively correlated with an indirectly estimated change in intracellular water (r(2)=0.79, P<0.05). We conclude that acute moderate dehydration down-regulates both total urea synthesis and its sensitivity to glucagon. The latter was related to estimated intracellular water loss. Dehydration may thus have nitrogen-saving consequences with regard to the hepatic contribution to whole-body nitrogen homoeostasis. The mechanism of this effect and the relationship with sodium and potassium fluxes is not known.

Acute pain induces insulin resistance in humans.

BACKGROUND: Painful trauma results in a disturbed metabolic state with impaired insulin sensitivity, which is related to the magnitude of the trauma. The authors explored whether pain per se influences hepatic and extrahepatic actions of insulin. METHODS: Ten healthy male volunteers underwent two randomly sequenced hyperinsulinemic-euglycemic (insulin infusion rate, 0.6 mU x kg(-1) x min(-1) for 180 min) clamp studies 4 weeks apart. Self-controlled painful electrical stimulation was applied to the abdominal skin for 30 min, to a pain intensity of 8 on a visual analog scale of 0-10, just before the clamp procedure (study P). In the other study, no pain was inflicted (study C). RESULTS: Pain reduced whole-body insulin-stimulated glucose uptake from 6.37+/-1.87 mg x kg(-1) x min(-1) (mean +/- SD) in study C to 4.97+/-1.38 mg x kg(-1) x min(-1) in study P (P < 0.01) because of a decrease in nonoxidative glucose disposal, as determined by indirect calorimetry (2.47+/-0.88 mg x kg(-1) x min(-1) in study P vs. 3.41+/-1.03 mg x kg(-1) x min(-1) in study C; P < 0.05). Differences in glucose oxidation rates were not statistically significant. The suppression of isotopically determined endogenous glucose output during hyperinsulinemia tended to be decreased after pain (1.67+/-0.48 mg x kg(-1) x min(-1) in study P vs. 2.04+/-0.45 mg x kg(-1) x min(-1) in study C; P = 0.06). Pain elicited a twofold to threefold increase in serum cortisol (P < 0.01), plasma epinephrine (P < 0.05), and serum free fatty acids (P < 0.05). Similarly, circulating concentrations of glucagon and growth hormone tended to increase during pain. CONCLUSIONS: Acute severe pain decreases insulin sensitivity, primarily by affecting nonoxidative glucose metabolism. It is conceivable that the counterregulatory hormonal response plays an important role. This may indicate that pain relief in stress states is important for maintenance of normal glucose metabolism.

Granulosa cell tumor of the ovary: a population-based study of 37 women with stage I disease.

OBJECTIVES: The goal of this work was to evaluate clinical and pathological findings, surgical procedures, and postoperative treatment in women with stage I granulosa cell tumor. METHODS: Data for 49 women with granulosa cell tumor were collected retrospectively. All pathological sections and findings were reviewed from diagnosis until recently. Follow-up data were collected from the general practitioner, hospital records, or death certificate. Fisher's exact test, Student's t test, Mann-Whitney test, and Kaplan-Meier survival analysis were applied, as appropriate. RESULTS: Thirty-seven women of median age 58 years (range, 33-82) were diagnosed in stage I. Follow-up time was 8 years (range, 8 months to 26 years). The estimated survival for stage I was 93% at 5 years, 84% at 10 years, and 62% at 20 years; the actual survival rates were 94, 82, and 62% after 5, 10, and 20 years, respectively. Primary treatment consisting of total abdominal hysterectomy and bilateral salpingo-oophorectomy was associated with improved survival (P < 0.05) and tended to be associated with longer relapse-free interval (P < 0.06). The 10-year survival rate was 40% in postmenopausal women operated conservatively and more than 90% for the extensively treated women (P < 0.05). Evidence of increased estrogen secretion was found more often in postmenopausal woman as compared with premenopausal women (P < 0.01) but did not affect survival. No pathological parameter correlated with prognosis. CONCLUSION: Granulosa cell tumor is a tumor of unquestionable malignant potential and has a tendency for late relapses. Long-time follow-up is recommended.

Acute non-traumatic pain increases the hepatic amino- to urea-N conversion in normal man.

BACKGROUND/AIM: Severe stress results in a catabolic state with nitrogen (N) loss via hepatic urea synthesis, and in most situations a sensation of pain. Our purpose was to establish whether pain per se upregulates liver function as to urea synthesis. METHODS: Ten healthy male volunteers were investigated on 3 occasions in a crossover design. Self-controlled electrical pain was applied to the abdominal skin for 30 min to an intensity of 8 on a visual analogue scale from 0 to 10. Next, the electric profile was reproduced during local analgesia (mepivacaine 2.5 mg/kg bw), and the pain was scored to only 0.5. Finally, there was a control experiment with no intervention. Alanine infusion (1 mmol/kg/h) was started 2 h before intervention and continued throughout the investigation. Urea-N synthesis rate (UNSR) was estimated hourly as urinary excretion corrected for accumulation in body water and gut hydrolysis. RESULTS: Pain increased the Functional Hepatic Nitrogen Clearance (FHNC) assessed by the ratio UNSR/AAN (in the 3 h following pain) by 20% (22.7+/-1.2 vs 19.0+/-0.7 l/h (control), p<0.05). FHNC during local analgesia was in between (21.1+/-1.1 l/h) but not significantly different from either of the two other experiments. Mean blood amino-N concentration (AAN) and mean UNSR were comparable in the three situations. There was no difference in serum glucagon among experiments, but pain increased serum cortisol (452+/-15 vs 233+/-20 nmol/l (control), p<0.001) and plasma adrenaline (104+/-16 vs 58+/-9 pg/ml (control), p<0.05). CONCLUSION: Acute, severe atraumatic pain induces an increase in the ability of the liver to convert amino- to urea-N, and thus acts as a catabolic stimulus via regulation of liver function. The measurements of known endocrine regulators of urea synthesis do not explain the phenomenon. The present data, however, suggest the hypothesis that the effects of pain were attenuated by local analgesia. If this is confirmed by further experiments, it would indicate a signal transmission to the liver which has not been previously described.

Acute pain induces an instant increase in natural killer cell cytotoxicity in humans and this response is abolished by local anaesthesia.

We have investigated the effect of pain without tissue injury on natural killer (NK) cell activity in peripheral blood in humans and the effect of local anaesthesia on the response. Ten subjects were investigated during two sessions. First, self-controlled painful electric stimulation was applied to abdominal skin for 30 min to an intensity of 8 on a visual analogue scale (0-10). Next, the electric intensity profile was reproduced during local anaesthesia (mepivacaine 10 mg ml-1 s.c. to a total dose of 2.5 mg kg-1). NK cell cytotoxicity was measured using a 4-h 51Cr-release assay against K562 target cells. NK cell activity increased from mean 22 (SEM 4)% (baseline) to 35 (6)% and 36 (5)% after 15 and 30 min of painful stimulation, respectively (P < 0.02). A simultaneous increase in the number of CD56+ cells in peripheral blood during pain was found. Stimulation after local anaesthesia did not change either NK cell activity or number. Parallel and significant increases in concentrations of plasma epinephrine and serum cortisol were observed. These changes were abolished by local anaesthesia. We conclude that acute severe pain without tissue injury markedly increased NK cell cytotoxicity. Local anaesthesia completely abolished this immunological and hormonal response.

Renal effects of a urodilatin infusion in patients with liver cirrhosis, with and without ascites.

This study reports the effects of a short-term (60 min) low-dose (20 ng x kg(-1) x min(-1)) infusion of synthetic urodilatin (URO) in patients with liver cirrhosis. URO is a natriuretic peptide. A total of 15 cirrhotic patients with ascites and nine without ascites participated in a randomized, double-blind, placebo-controlled study in a crossover design. Renal hemodynamics were estimated by a clearance technique using radioactive tracers, and tubular handling of sodium was evaluated by the lithium clearance method. The renal effects of URO were characterized by a significant increase in urine sodium excretion rate (UNa) and urine flow rate (V) in the cirrhotic patients without ascites (UNa: 173%; V: 94%) and with ascites (UNa: 219%, P < 0.01; V: 42%, P < 0.01) when compared with placebo infusions. Fractional excretion of sodium increased significantly, indicating a tubular effect of URO on sodium handling. Filtration fraction, lithium clearance (a marker of end-proximal fluid delivery), and fractional excretion of lithium increased, fractional proximal tubular sodium reabsorption decreased, and absolute proximal tubular sodium reabsorption remained unchanged, suggesting increased delivery of isotonic fluid from the proximal tubule during URO infusion. In addition, a significant decrease in fractional distal tubular sodium reabsorption contributed to the natriuresis. In conclusion, URO improved sodium and urine output in cirrhotic patients with and without ascites by enhancing fluid delivery from the proximal tubules in addition to inhibiting fractional sodium reabsorption in the distal nephron.