A novel isotonic-balanced electrolyte solution with 1% glucose for intraoperative fluid therapy in children: results of a prospective multicentre observational post-authorization safety study (PASS)

Background: The recommendations for intraoperative fluid therapy in children have been adapted from hypotonic to isotonic electrolyte solutions with lower glucose concentrations (1–2.5% instead of 5%) to avoid hyponatremia and hyperglycemia. Objective: The objective of this prospective multicentre observational post‐authorization safety study was to evaluate the intraoperative use of a novel isotonic‐balanced electrolyte solution with 1% glucose (BS‐G1) with a particular focus on changes in acid–base status, electrolyte and glucose concentrations. Methods: Following local ethics committee approval, pediatric patients aged up to 4 years with an ASA risk score of I–III undergoing intraoperative administration of BS‐G1 were enrolled. Patient demographics, the performed procedure, adverse drug reactions, hemodynamic data, and the results of blood gas analysis before and after infusion were documented with a focus on changes in acid–base status, electrolyte and glucose concentrations. Results: In 107 patients (ASA I–III; age 16.2 ± 15.4, range day of birth to 47.7 months; body weight 8.8 ± 4.8, range 1.6–18.8 kg), the mean volume infused was 20 ± 12.6 (range 3.6–83.3) ml·kg^?1 BS‐G1. During the infusion, hemoglobin, hematocrit, anion gap, strong ion difference, and calcium decreased and chloride and glucose increased significantly within the physiologic range. All other measured parameters including sodium, bicarbonate, base excess, and lactate remained stable. Neither hypoglycemia (glucose <2.5 mmol·l^?1) nor hyperglycemia (glucose >10 mmol·l^?1) was documented after BS‐G1 infusion. No adverse drug reactions were reported. Conclusion: The studied isotonic‐balanced electrolyte solution with 1% glucose helps to avoid perioperative acid–base imbalance, hyponatremia, hyperglycemia, and ketoacidosis in infants and toddlers and may therefore enhance patient safety.     

Changes in acid-base, electrolyte and hemoglobin concentrations during infusion of hydroxyethyl starch 130/0.42/6 : 1 in normal saline or in balanced electrolyte solution in children

Introduction: A balanced volume replacement strategy is a well established concept for correcting hypovolemia using plasma adapted isotonic crystalloid solutions with a physiological electrolyte pattern and acetate as bicarbonate precursor. Recently, third‐generation hydroxyethyl starch (HES) has also become available in a balanced electrolyte solution instead of normal saline. Therefore, in this prospective non‐interventional clinical study, the perioperative administration of HES 130/0.42/6 : 1 in normal saline (ns‐HES) and in balanced electrolyte solution (bal‐HES) was evaluated in children with a focus on acid‐base, electrolyte and hemoglobin changes. Methods: Following local ethics committee approval, pediatric patients aged up to 12 years with an ASA risk score of I–III undergoing perioperative administration of HES (ns‐HES from May 2006 to December 2007, bal‐HES from January 2008 to January 2009) were included. Patient demographics, the performed procedure, adverse drug reactions, hemodynamic data and the results of blood gas analysis were documented with a focus on changes in acid‐base, electrolyte and hemoglobin concentrations. Results: Of 396 enrolled patients (ASA I–III; age 2.3 ± 3, range day of birth – 12 years; body weight 10.8 ± 9, range 0.9–52 kg), 249 received ns‐HES and 147 bal‐HES (mean volume infused 9.9 ± 4 and 9.4 ± 6.9 ml·kg^?1, respectively). After HES infusion, hemoglobin decreased in both groups, whereas bicarbonate and base excess (BE) decreased only with ns‐HES and remained stable with bal‐HES (BE before infusion: ns‐HES ?1.8 ± 2.8, bal‐HES ?1.7 ± 2.7 mmol·l^?1; after infusion: ns‐HES ?2.6 ± 2.4; bal‐HES ?1.6 ± 2.6 mmol·l^?1, P < 0.05). Chloride (Cl) concentrations increased in both groups and were significantly higher with ns‐HES (Cl before infusion: ns‐HES 105.6 ± 3.7, bal‐HES 105.1 ± 2.8 mmol·l^?1; after infusion: ns‐HES 107.7 ± 3.2, bal‐HES 106.3 ± 2.9 mmol·l^?1, P < 0.01). No serious adverse drug reactions were observed. Conclusion: Infusion related iatrogenic acid‐base and electrolyte alterations can be minimized by using hydroxyethyl starch in a balanced electrolyte solution instead of normal saline.     

A novel isotonic balanced electrolyte solution with 1% glucose for intraoperative fluid therapy in neonates: results of a prospective multicentre observational postauthorisation safety study (PASS)

Background: Neonates have a higher metabolic rate and an increased risk of perioperative hypoglycemia and lipolysis, but during anesthesia, both oxygen consumption and metabolic rate are decreased, and this may lead to reduced intraoperative glucose requirements. Objective: The objective of this prospective multicentre observational postauthorisation safety study was to evaluate the intraoperative use of a novel isotonic balanced electrolyte solution with a low glucose concentration of 1% (BS‐G1) in neonates with a particular focus on changes in acid‐base, electrolyte, and glucose concentrations. Methods: Following the local ethics committee approval, neonates with a postmenstrual age under 45 weeks and an ASA risk score of I–IV undergoing intraoperative administration of BS‐G1 were enrolled. Patient demographics, the performed procedure, adverse drug reactions, hemodynamic data, and the results of blood gas analysis before and after infusion were documented with a focus on changes in acid‐base, electrolyte, and glucose concentrations. Results: In 66 neonates (ASA I–IV; postmenstrual age 38 ± 4, range 25–45 weeks; body weight 2.9 ± 0.9, range 0.65–4.6 kg), the mean infusion rate was 10.4 ± 3.2 (range 4.5–19.6) ml·kg^?1·h^?1 BS‐G1. During the infusion, hemoglobin, hematocrit, bicarbonate, base excess, anion gap, strong ion difference, and calcium decreased, and chloride and glucose increased significantly within the physiological range. All other measured parameters including sodium and lactate remained stable. Neither hypoglycemia (glucose < 3 mm ) nor hyperglycemia (glucose > 10 mm ) was documented after BS‐G1 infusion. No adverse drug reactions were reported. Conclusion: The study shows that the intraoperative use of an isotonic balanced electrolyte solution with 1% glucose and a mean infusion rate of 10 ml·kg^?1·h^?1 helps to avoid acid‐base dysbalance, hyponatraemia, hypoglycemia, ketoacidosis, and hyperglycemia in surgical neonates. A careful intraoperative monitoring and adaptation of the infusion rate as needed is crucial because the glucose and fluid requirements may vary widely between subjects.     

Alterations of acid-base balance, electrolyte concentrations, and osmolality caused by nonionic hyperosmolar contrast medium during pediatric cardiac catheterization

Objective: This prospective clinical observational study was conducted to investigate the effects of contrast medium on acid–base balance, electrolyte concentrations, and osmolality in children. Background:  For pediatric cardiac catheterization, high doses of nonionic hyperosmolar contrast medium are widely used. Methods: Forty pediatric patients (age 0–16 years) undergoing cardiac angiography with more than 3 ml·kg^?1 of nonionic hyperosmolar contrast medium (Iomeprol) were enrolled, and the total amount of the contrast agent given was documented. Before and after contrast medium administration, a blood sample was collected to analyze electrolytes, acid–base parameters, osmolality, hemoglobin, and hematocrit. Results: After cardiac catheterization, pH, hemoglobin, hematocrit, bicarbonate, base excess, sodium, chloride, calcium, anion gap and strong ion difference decreased, whereas osmolality increased significantly (base excess ?1.8 ± 1.8 vs ?3.4 ± 2.3, sodium 138 ± 2.9 vs 132 ± 4.1 mm , osmolality 284 ± 5.7 vs 294 ± 7.6 mosmol·kg^?1, P < 0.01). Seventy‐eight percent of the children developed hyponatremia (sodium <135 mm ). No changes were seen in pCO₂, lactate, and potassium levels. Conclusions: Regarding the differential diagnosis of metabolic disturbances after pediatric cardiac catheterization, low‐anion gap metabolic acidosis and hyponatremia should be considered as a possible side effect of the administered contrast medium.     

Hydroxyethyl starch 130/0.42/6:1 for perioperative plasma volume replacement in children: preliminary results of a European Prospective Multicenter Observational Postauthorization Safety Study (PASS)

Background: Several clinical studies have shown that hydroxyethyl starch (HES) may be as effective and safe as, but less expensive than, albumin when used for perioperative plasma volume replacement (PVR) in children. The new third generation HES 130/0.42 solution was designed to reduce adverse drug reactions (ADRs) and improve safety while maintaining efficacy. Therefore, the objective of this prospective multicenter observational postauthorization safety study (PASS) was to evaluate the perioperative use of HES 130/0.42 in 1000 children with a particular focus on possible ADRs. Methods: Approximately 300 of 1000 pediatric patients aged up to 12 years with ASA risk scores of I–III receiving perioperative HES 130/0.42 (Venofundin 6%; Braun, Melsungen, Germany) should be enrolled for interims analysis in the first year. The statistical sample size calculation showed that this number of patients would be sufficient to detect a 1% incidence of ADRs. Following approval by local ethics committee, patient demographics, data relating to HES 130/0.42 use, the procedures performed, anesthesia, and ADRs were documented with a particular focus on cardiovascular stability, hemodilution, acid–base balance, renal function, blood coagulation, and hypersensitivity. Results: Three hundred and sixteen children (ASA I–III, age 3 ± 3.4 [range, day of birth–12 years], body weight 13 ± 10.5 [range, 1.1–60 kg]) were studied at five centers in Germany, Austria, and Italy from May 2006 until August 2007. Forty‐five percent of the patients underwent abdominal surgery, 12.4% urologic procedures, 11.4% thoracic surgery, 7.6% orthopedic procedures, and 7% cardiovascular surgery. The mean volume of infused HES 130/0.42 was 11 ± 4.8 ml·kg^?1 (range, 5–42). Cardiovascular stability was maintained in all cases. After HES infusion, hemoglobin (11.5 vs 10.25 g·dl^?1), base excess (?2 vs ?2.7 mmol·l^?1), anion gap (12.9 vs 11.2 mmol·l^?1), and strong ion difference (34.3 vs 31.4 mmol·L^?1) decreased, and chloride (105.7 vs 107.8 mmol·l^?1) increased significantly (P < 0.05). No serious ADRs (i.e., anaphylactoid reaction, renal failure, clotting disorders) were observed. Conclusion: Moderate doses of HES 130/0.42 help to maintain cardiovascular stability and lead to only moderate changes in hemoglobin concentration and acid–base balance in children. The probability of serious ADRs is lower than 1%. Therefore, HES 130/0.42 for PVR seems to be safe and effective even in neonates and small infants with normal renal function and coagulation.     

Cystatin C: influence of perfusion and myocardial injury on early (<24 h) renal function after pediatric cardiac surgery

Background: Cardiopulmonary bypass (CPB)‐associated renal dysfunction following cardiac surgery is well recognized. In patients with renal disease, cystatin C has emerged as a new biomarker which in contrast to creatinine (Cr) is sensitive to minor changes in glomerular filtration rate (GFR). Aim: We utilized cystatin C to investigate the association of CPB perfusion parameters with acute renal injury after pediatric cardiac surgery. Methods: Twenty children, aged 4–58 months (AVSD, n = 7; VSD, n = 9; and ASD, n = 4), were prospectively studied. Glomerular filtration rate was quantified postoperatively by creatinine clearance (first and second 12‐h periods; CrCl_0–12 and CrCl_12–24). Serum cystatin C and Cr were measured preoperatively and on days 0–3. Recorded CPB parameters included bypass duration (BP), perfusion pressure (PP), lowest pump flow (Q_min), lowest hematocrit, and corresponding lowest oxygen delivery (DO_{2 min}). Myocardial injury was determined by troponin‐I. Results: Postoperatively, GFR remained unchanged (CrCl_0–12 63.6 ± 37.0 vs CrCl_12–24 65.1 ± 27.5; P = 0.51) and only correlated with cystatin C (CrCl_0–12 vs cystatin C_Day0 [r = 0.58, P = 0.018] and Cr_Day0 [r = 0.09, P = 0.735]). Cr and cystatin C increased postoperatively to peak on days 2 and 3, respectively (Cr_PreOp 31 ± 6.9 vs Cr_Day2 36.9 ± 12.2, P = 0.03; cystatin C_Day0 0.83 ± 0.27 vs cystatin C_Day3 1.45 ± 0.53, P = 0.02). Increased cystatin C was significantly associated with BP (P = 0.001), mean PP (P = 0.029), Q_min (P = 0.005), troponin‐I (P < 0.001), and DO_2min <300 ml·min^?1·m^?2 (P = 0.007). Receiver–operator cutoff >1.044 mg·l^?1 for cystatin C exhibited 100% sensitivity and 67% specificity for detecting renal dysfunction, defined as GFR <55 ml·min^?1·1.73 m^?2. Conclusions: Cystatin C is a sensitive marker of early renal dysfunction following pediatric heart surgery. Variations in bypass parameters, myocardial injury, and ultimately critical oxygen delivery are significantly associated with the degree of renal impairment.     

Phenylephrine in treating maternal hypotension due to spinal anaesthesia for caesarean delivery: effects on neonatal catecholamine concentrations, acid base status and Apgar scores

Maternal and neonatal catecholamine concentrations, following the use of either phenylephrine or ephedrine to treat a drop in maternal blood pressure after spinal anaesthesia for caesarean delivery, were compared. Patients were randomly assigned to one of two groups: Group 1 patients (n = 20) were treated with ephedrine given as 5 mg intravenous bolus injections; Group 2 patients (n = 20) were treated with phenylephrine given as 40 μg intravenous bolus injections, for decreases in maternal systolic blood pressure to maintain maternal systolic blood pressure above 100 mmHg. Maternal vein (MV), umbilical vein (UV), and umbilical artery (UA) blood samples were taken at the time of delivery. Samples were analyzed for catecholamine concentrations and blood gas values. Noradrenaline concentrations in UA, UV and MV (at delivery) samples were significantly higher in group 1 compared to group 2; they were 6858±3689 vs 1674±944-pg · ml^-1 (P<0.0001), 1265±758 vs 395±470 pg · ml^-1 (P<0.001) and 239±165 vs 103±93 pg · ml^-1 (P<0.01), respectively. Comparing blood gas values between groups 1 and 2, statistically significant differences were observed in UA pH (7.28±0.01 and 7.32±0.01 pH units, P=0.01), UA pCO₂ (7.32±0.24 and 6.68±0.21 kPa, P=0.03), UA base excess (2.2±0.4 and 0.9±0.4 mmol · l^-1, P=0.04) and UV base excess (2.0±0.3 and 0.7±0.3 mmol · l^-1, P=0.004). No significant differences in maternal characteristics, acid base values, incidence of nausea and vomiting, and Apgar scores were observed between groups. Phenylephrine appears to be as safe and effective as ephedrine in treatment of drop in blood pressure in healthy non-labouring parturients undergoing caesearean delivery. The use of phenylephrine was also associated with significantly lower noradrenaline concentrations in both mother and neonate.     

Effect of 830 nm low-level laser therapy applied before high-intensity exercises on skeletal muscle recovery in athletes

Our aim was to investigate the immediate effects of bilateral, 830 nm, low-level laser therapy (LLLT) on high-intensity exercise and biochemical markers of skeletal muscle recovery, in a randomised, double-blind, placebo-controlled, crossover trial set in a sports physiotherapy clinic. Twenty male athletes (nine professional volleyball players and eleven adolescent soccer players) participated. Active LLLT (830 nm wavelength, 100 mW, spot size 0.0028 cm², 3–4 J per point) or an identical placebo LLLT was delivered to five points in the rectus femoris muscle (bilaterally). The main outcome measures were the work performed in the Wingate test: 30 s of maximum cycling with a load of 7.5% of body weight, and the measurement of blood lactate (BL) and creatine kinase (CK) levels before and after exercise. There was no significant difference in the work performed during the Wingate test (P?>?0.05) between subjects given active LLLT and those given placebo LLLT. For volleyball athletes, the change in CK levels from before to after the exercise test was significantly lower (P?=?0.0133) for those given active LLLT (2.52 U l^?1 ± 7.04 U l^?1) than for those given placebo LLLT (28.49 U l^?1 ± 22.62 U l^?1). For the soccer athletes, the change in blood lactate levels from before exercise to 15 min after exercise was significantly lower (P?<?0.01) in the group subjected to active LLLT (8.55 mmol l^?1 ± 2.14 mmol l^?1) than in the group subjected to placebo LLLT (10.52 mmol l^?1 ± 1.82 mmol l^?1). LLLT irradiation before the Wingate test seemed to inhibit an expected post-exercise increase in CK level and to accelerate post-exercise lactate removal without affecting test performance. These findings suggest that LLLT may be of benefit in accelerating post-exercise recovery.     

The effect of anti‐emetic doses of dexamethasone on postoperative blood glucose levels in non‐diabetic and diabetic patients: a prospective randomised controlled study

There are few data regarding postoperative hyperglycaemia in non‐diabetic compared with diabetic patients following postoperative nausea and vomiting prophylaxis with dexamethasone. Eighty‐five non‐diabetic patients and patients with type‐2 diabetes were randomly allocated to receive intravenous dexamethasone (8 mg) or ondansetron (4 mg). Blood glucose levels were measured at baseline and then 2, 4 and 24 h following induction of anaesthesia. In non‐diabetic patients, the mean (SD) maximum blood glucose was higher in those who received dexamethasone compared with ondansetron (9.1 (2.2) mmol.l^?1 vs. 7.8 (1.4) mmol.l^?1, p = 0.04). In diabetic patients, the mean (SD) maximum blood glucose was also higher in those who received dexamethasone compared with ondansetron (14.0 (2.5) mmol.l^?1 vs. 10.7 (2.4) mmol.l^?1, p < 0.01). Multivariate analysis demonstrated that dexamethasone administration was a significant predictor of maximum postoperative blood glucose increase (p < 0.01) after adjusting for potential confounders. There was no interaction between baseline blood glucose level, or presence or absence of diabetes, and dexamethasone administration. We conclude that dexamethasone increases postoperative blood glucose levels in both non‐diabetics and diabetics.     

Hemostatic consequences of a non-fresh or reconstituted whole blood small volume cardiopulmonary bypass prime in neonates and infants

Objectives: Despite aggressive measures to miniaturize the cardiopulmonary bypass (CPB) circuit in neonates and infants, the CPB prime volume is often at least as large as the patients’ blood volume. We conducted an observational study to characterize the hemostatic consequences of a CPB prime consisting of either non‐fresh or reconstituted whole blood. Methods: Hematocrit, fibrinogen, platelet count, plasminogen, anti‐thrombin III (AT‐III), and factors (F) II, V, VII, IX, and X of 30 neonates and infants undergoing cardiac surgery with CPB utilizing either a non‐fresh or reconstituted whole blood prime were prospectively evaluated at eight time points. Following protamine administration, microvascular bleeding was treated by protocol. Results: The hemostatic composition of the CPB prime was the same following the use of either non‐fresh or reconstituted whole blood. The CPB prime platelet count (mean ± sd ) was 5.87 ± 2.84 × 10³ μl^?1 when compared to a preoperative platelet count of 298 ± 142 × 10³ μl^?1 (P < 0.0001). Twenty patients received 17.3 ± 9.2 ml·kg^?1 (0.86 ± 0.46 units·kg^?1) of platelets with significant improvement in platelet count. Nine patients received 16.7 ± 13.4 ml·kg^?1 (0.84 ± 0.67 units·kg^?1) of cryoprecipitate with significant improvements in FVIII and fibrinogen. Conclusions: Non‐fresh or reconstituted whole blood as a component of a small volume CPB prime in neonates and infants induces clinically significant dilutional thrombocytopenia in conjunction with less significant reductions in fibrinogen, FII, FV, FVII, FVIII, FIX, FX, plasminogen, and AT‐III.     

Testosterone and high‐sensitive C‐reactive protein in coronary artery disease patients awaiting coronary artery bypass graft

Natural androgens inhibit atherosclerosis in men. This study aimed to examine whether testosterone and high‐sensitive C‐reactive protein differ between patients with coronary artery disease and those without coronary artery disease and to determine the association with the severity of coronary artery disease. Two hundred and six male subjects were recruited. Serum total testosterone and high‐sensitive C‐reactive protein were estimated. Severity of coronary artery disease was assessed by angiographic scores. Total testosterone level in patients was significantly different from controls (11.4 ± 2.7 vs. 18.1 ± 7.2 nm P = 0.001) and high‐sensitive protein level in cases was significantly higher compared to controls (3.37 ± 1.62 mg l^?1 vs. 1.71 ± 0.60 mg l^?1, P = 0.001). Testosterone levels were not significantly different with vessel (P = 0.592), Leaman (P = 0.694) and Gensini (P = 0.329) score groups, but high‐sensitive C‐reactive protein showed significant positive correlation among the respective groups (P = 0.005, P = 0.028, P = 0.015). Testosterone was lower, while high‐sensitive C‐reactive protein was higher in patients compared to controls. Testosterone showed no correlation with the severity of atherosclerosis, but high‐sensitive C‐reactive protein showed significant positive correlation.     

The relationship between morphology, motility and zona pellucida binding potential of human spermatozoa

Summary. Prediction of the fertilizing potential of human gametes under in vitro conditions has been a major field of interest of assisted reproductive programmes. However, sperm morphology has been regarded as a predictor of human in vitro fertilization rate. This paper prospectively evaluates the relationships among normal sperm morphology and (1) motion characteristics viz. curvilinear velocity (VCL), straight line velocity (VSL), and linearity (LIN) (n = 37) and (2) spermzona pellucida binding capacity under HZA conditions (n = 144) of two separate groups of infertile couples. Semen was evaluated for sperm concentration, percentage motility, forward progression, and percentage normal morphology (strict criteria). The motility characteristics were measured using a computerized Sperm Motility Quantifier (SMQ). The zona binding potential of sperm was evaluated using the hemizona assay. Firstly, the VCL significantly differred between the P-pattern and both the G (72.9 ± 7 vs. 86.3±16 μm s^?1; P = 0.04) and N patterns (72.9 ± 7 vs. 91.0 ± 15 μm s^?1; P = 0.002). The VSL differed only between the P and N patterns, being 19.7 ± 7 vs. 32.6±15 μm s^?1 (P = 0.02), respectively. No significant differences in LIN were noted between any of the three patterns. The sperm concentration differed significantly between the P and both the G (37.9±35 vs. 80.8 ± 9 × 10⁶ ml^?1; P = 0.03) and the N patterns (37.9 ± 35 vs. 89.7 ± 72 × 10⁶ ml^?1; P = 0.05). Significant differences were observed in the percentage motility between the P and both the G (38.0 ± 21% vs. 43.7 ±9%; P = 0.03) and the N patterns (38.0 ± 21% vs. 52.1±8%; P = 0.04). In the second study, the hemizona indices (HZI) differed significantly between the P and both the G (29.3 ± 26% vs. 57.6 ± 62%; P = 0.01) and the N patterns (29.3 ± 26% vs. 102.4 ± 80%; P < 0.001). The G and N patterns also differed significantly in their HZI (57.6 ± 62% vs. 102.4 ± 80%; P = 0.005). Sperm concentration differed between the P and both the G (32.8 ± 29 vs. 76.1±54 × 10⁶ ml^?1; P < 0.001) and the N patterns (32.8 ± 29 vs. 95.44 ± 61 × 10⁶ ml^?1; P < 0.001). The percentage motility differs significantly between the P pattern and both the G (41.2± 17% vs. 50.9±11%; P = 0.002) and the N patterns (41.2±17% vs. 53.4±11%; P = 0.001). Sperm morphology seems to be indicative of important functional characteristics of spermatozoa, for example motility and zona pellucida binding.     

Randomised double‐blinded comparison of phenylephrine vs ephedrine for maintaining blood pressure during spinal anaesthesia for non‐elective Caesarean section*

In a randomised, double‐blinded study, we compared boluses of phenylephrine 100 μg with ephedrine 10 mg for treating hypotension (systolic blood pressure < 100 mmHg) in 204 patients having non‐elective Caesarean section under spinal anaesthesia. Umbilical arterial (UA) and venous (UV) pH and base excess were similar between groups. In the ephedrine group, UA lactate concentration was higher (median 2.6 [interquartile range 2.3–3.3] vs 2.4 [1.9–3.0] mmol.l^?1, p = 0.002) and UV lactate concentration was higher (2.5 [2.2–3.2] vs 2.3 [1.9–2.8] mmol.l^?1, p = 0.016) and more patients had nausea or vomiting (12.7% vs 3.9%, p = 0.02). Clinical neonatal outcome was similar. Of the protocol‐compliant patients (n = 148), UA Po ₂ and UV Po ₂ were lower in the phenylephrine group although oxygen content was similar. We conclude that phenylephrine and ephedrine are both suitable vasopressors for use in non‐elective Caesarean sections.     

Hemodynamic effects of dobutamine and dopexamine after cardiopulmonary bypass in pediatric cardiac surgery*

Background: After surgical repair of congenital heart disease, inotropic support is sometimes necessary to wean from cardiopulmonary bypass. In pediatric cardiac surgery, dobutamine and dopamine are often used as inotropic support. Dopexamine is a synthetic catecholamine, which has positive inotropic and vasodilating properties. Because the hemodynamic effects of catecholamines are modified after cardiopulmonary bypass, the aim of this study was to investigate the effects of dobutamine and dopexamine on cardiac index and systemic vascular resistance index after cardiopulmonary bypass in pediatric cardiac surgery. Methods: The study was performed in a prospective, randomized, and double‐blinded cross‐over design. The investigation included 11 children for elective, noncomplex congenital heart surgery. After weaning from cardiopulmonary bypass and a 20‐min period of steady state, children received either 2.5 μg·kg^?1·min^?1 dobutamine or 1 μg·kg^?1·min^?1 dopexamine for 20 min. Cardiac index (transpulmonary thermodilution), mean arterial pressure, central venous pressure, stroke volume, systemic vascular resistance, and central venous oxygen saturation were determined. The primary outcome variable was cardiac index. Results: No difference in cardiac index was observed between the two groups (P = 0.594). Both drugs increased cardiac index, dopexamine from 3.9 ± 0.6 to 4.7 ± 0.8 l·min^?1·m^?2 (P = 0.003) and dobutamine from 4.1 ± 0.7 to 4.8 ± 0.7 l·min^?1·m^?2 (P = 0.004). During treatment with dobutamine, children presented with significantly higher mean arterial pressure (P = 0.003) and systemic vascular resistance index (P = 0.026). Conclusions: This trial demonstrates that low‐dose dobutamine and dopexamine both increase cardiac index during pediatric cardiac surgery but with different hemodynamic effects.     

Adrenocorticotrophic hormone,cortisol and catecholamine concentrations during insulin hypoglycaemia in dogs anaesthetized with thiopentone

Glucose homeostasis is maintained by complex neuroendocrine control mechanisms. Increases in plasma concentrations of various glucose-raising hormones such as glucagon, catecholamines, adrenocorticotrophic hormone (ACTH), and cortisol are observed under certain conditions associated with stress (haemorrhage and hypoglycaemia). The purpose of this study was to determine the effect of thiopentone anaesthesia on the cathecholamine, ACTH and cortisol response to insulin hypoglycaemia in dogs. Blood sugar (BS), plasma cathecholamine, and ACTH, and serum cortisol concentrations were measured during the course of (1) an intravenous insulin test (ITT) and (2) an ACTH test in conscious and in anaesthetized fasted dogs. During the ITT, the anaesthetized dogs showed a moderate resistance, compared with conscious dogs, to the hypoglycaemic action induced by insulin (blood sugar concentration 30 min after insulin injection: 2.91 ± 0.25 vs 1.93 ± 0.12 mM · L^?1; P < 0.01). In addition, decreased epinephrine (220 ± 27 vs 332 ± 32 pg · ml^?1 ACTH (65 ± 6 vs 90 ± 5 pg · ml^?1) and cortisol (4.48 ± 0.3 vs 6.25 ± 0.5 μg · ml^?1) concentrations were detected 60 min after insulin injection (P < 0.01). The norepinephrine response to hypoglycaemia was not altered by anaesthesia (273 ± 33 vs 325 ± 25 pg · ml^?1). Anaesthetized dogs showed a decreased cortisol response to ACTH at 45 min (5.68 ± 0.54 vs 8.87 ± 0.47 μg · ml^?1) when compared with control dogs (P < 0.001). Haemodynamic variables during anaesthesia showed little changes (P < NS); while respiratory rate was altered (P < 0.01 between 60 and 105 min). Arterial pH was decreased (7.29 ± 0.03 vs 7.36 ± 0.04; P < 0.05) and PaCO₂ was increased (6.8 ± 0.3 vs 5.2 ± 0.3; P < 0.01) at 30 min from induction of anaesthesia but little change was seen after the beginning of the ITT and ACTH tests. We conclude that thiopentone anaesthesia provokes a moderate resistance to the hypoglycaemic action of insulin. This does not appear to be related to increases in plasma concentrations of cathecholamines, cortisol or ACTH. Since the hyperglycaemic effects of cathecholamines and glucagon are synergistic it is possible that glucagon plays an important role in the altered blood sugar response to insulin administration.     

Effect of the SK/IK channel modulator 4,5-dichloro-1,3-diethyl-1,3-dihydro-benzoimidazol-2-one (NS4591) on contractile force in rat, pig and human detrusor smooth muscle

What’s known on the subject? and What does the study add? Increased urinary bladder detrusor smooth muscle phasic contractility has been suggested to be associated with idiopathic bladder overactivity. Small conductance Ca2⁺‐activated K⁺ (SK 1–3) channels have attracted considerable interest as putative target for new therapeutic strategy for treating overactive bladder. These channels play an important role in regulating the function and activity of urinary bladder smooth muscle (UBSM), and the loss of SK channel function has been shown to increase UBSM excitability and contractility. However, it is not known whether activation of SK channels has the converse effect of reducing UBSM excitability and contractility. In this paper, we investigated this possibility in the rat, pig and human UBSM by using the novel SK channel opener NS4591. These studies demonstrate that the SK channel modulator NS4591 has a potential role as a pharmacological tool to study the involvement of SK (and IK) channels in mammals and rodents urinary bladder. NS4591 may have therapeutic potential for treatment of detrusor overactivity.

OBJECTIVE

• ? To investigate the importance of small (SK)‐ and intermediate (IK)‐conductance Ca2⁺‐activated K⁺ channels on bladder function, by studying the effects of 4,5‐dichloro‐1,3‐diethyl‐1,3‐dihydro‐benzoimidazol‐2‐one (NS4591), a new modulator of SK/IK channels, on contractions induced by electrical field stimulation (EFS) and carbachol in rat, pig and human detrusor.

PATIENTS AND METHODS

• ? Detrusor biopsies were obtained from rats, pigs and male patients undergoing cystectomy because of bladder cancer.
• ? Force was recorded using myographs.
• ? Intracellular free Ca²⁺ was measured in myocytes using microfluorimetry.

RESULTS

• ? In rat bladder rings subjected to EFS, cumulative addition of NS4591 (0.1–30 µM) decreased force by 82 ± 2.9% (n = 6).This effect was reduced by 64 ± 5.2% in the presence of 0.3 µM apamin, a specific inhibitor of SK channels. Apamin increased the force evoked by EFS significantly: force was increased by 14.2 ± 3.4% (n = 5) and 10.1 ± 2.6% (n = 7) in pig and human detrusor strips, respectively (P = 0.04 and P = 0.02).
• ? The cumulative addition of NS4591 (0.3–30 µM) significantly reduced the amplitude of carbachol‐induced rhythmic oscillations by 62.0 ± 12.0% (n = 12) and the minimum force between oscillations by 30 ± 5% (n = 9) in pig detrusor strips (P < 0.005). In the presence of 10 µM NS4591, carbachol (1 µM) induced rhythmic contractions with an amplitude and normalized mean power frequency (nmeanPF) of 8.4 ± 5.1% and 0.11 ± 0.06 mN root mean square (rms) Hz (n = 12), respectively, vs. 21 ± 3.4% and 0.17 ± 0.04 mN rms Hz in control strips (n = 13). Apamin induced 6‐ and 11‐fold increases in amplitude and nmeanPF vs. 1.3‐ and 2‐fold increases in control strips.
• ? In human detrusor strips (n = 15), the cumulative addition of NS4591 (1–30 µM) significantly reduced the amplitude by 69 ± 11%, the nmeanPF by 78 ± 6% and the minimum force between carbachol‐induced oscillations by 59 ± 5% (P < 0.008). The addition of apamin (0.3 µM) before application of 1 µM carbachol abolished the effects of NS4591 on amplitude and partially abolished its effect on nmeanPF by 41 ± 7%, vs. a 78 ± 6% reduction in the absence of apamin (n = 8).
• ? In spontaneously active detrusor preparations, NS4591 reduced or abolished contractions.
• ? Furthermore, NS4591 (10 µM) decreased the carbachol‐induced increase in the fura‐2 ratio by 43 ± 3% compared with control (n = 12) (P < 0.03).

CONCLUSIONS

• ? The SK/IK channel modulator NS4591 inhibits EFS‐ and carbachol‐induced contractions in rat, pig and human detrusor muscle.
• ? NS4591 may have therapeutic potential for treatment of detrusor overactivity.

     

Cerebral metabolism during deep hypothermic circulatory arrest vs moderate hypothermic selective cerebral perfusion in a piglet model: a microdialysis study

Background: Few data exist regarding antegrade selective cerebral perfusion (ASCP) and its application in newborn and juvenile patients. Clinical data suggest ASCP alone to be superior to deep hypothermic circulatory arrest (DHCA); however, the effects of moderate hypothermia during ASCP on cerebral metabolism in this patient population are still unclear. Methods: After obtaining the approval from animal investigation committee, 16 piglets were randomly assigned to circulatory arrest combined with either ASCP at 27°C or DHCA at 18°C for 90 min. Cerebral oxygen extraction fraction (COEF) from blood as well as cerebral tissue glucose, glycerol, lactate, pyruvate, and the lactate/pyruvate ratio (L/P ratio) by microdialysis were obtained repeatedly. Results: COEF was lower during cooling and rewarming, respectively, in the DHCA18 group compared to the ASCP27 group (30 ± 8 vs 56 ± 13% and 35 ± 6 vs 58 ± 7%, respectively). Glucose decreased in both the DHCA18 and ASCP27 groups during the course of cardiopulmonary bypass (CPB), but were higher in the ASCP27 group during ASCP, compared to the DHCA18 group during circulatory arrest (0.7 ± 0.1 vs 0.2 ± 0.1 mm ·l^?1, P < 0.05). Pyruvate was higher (ASCP27 vs DHCA18: 53 ± 17 vs 6 ± 2 μm ·l^?1, P < 0.05), and the L/P ratio increased during circulatory arrest in the DHCA18 group, compared to the selective perfusion phase of the ASCP27 group (DHCA18 vs ASCP27: 1891 ± 1020 vs 70 ± 28, P < 0.01). Conclusions: In this piglet model, both cerebral oxygenation and microdialysis findings suggested a depletion of cerebral energy stores during circulatory arrest in the DHCA18 group, compared to selective cerebral perfusion combined with circulatory arrest in the ASCP27 group.     

Comparison of propofol versus propofol‐ketamine combination for sedation during spinal anesthesia in children: randomized clinical trial of efficacy and safety

Objectives: This study was designed to compare the efficacy and safety of propofol vs propofol‐ketamine combination for sedation during pediatric spinal anesthesia. Methods: Forty children, aged 3–8 undergoing spinal anesthesia for lower abdominal surgeries were included. Participants were randomly assigned into two groups. Group 1 received propofol bolus of 2 mg·kg^?1 followed by an infusion of 4 mg·kg^?1·h^?1. Group 2 received a combination of 1.6 mg·kg^?1 propofol and 0.4 mg·kg^?1 ketamine followed by an infusion of 3.2 mg·kg^?1·h^?1 and 0.8 mg·kg^?1·h^?1, respectively. The infusion rate was titrated to keep the child sedated at University of Michigan Sedation Score of 3. The heart rate, blood pressure, respiratory rate and oxygen saturation were recorded every 5 min. The episodes of spontaneous body movements and requirement of supplemental sedation were recorded. The postoperative recovery was assessed by modified Aldrette score. Results: Seventeen patients in group 1 and four patients in group 2 (P < 0.001) required extra boluses of study drug to prevent movements during lumbar puncture. Four patients experienced respiratory depression and three airway obstruction in group 1 when compared to one patient each in group 2 (P < 0.05). The recovery time was similar in both groups. None of the patient had postoperative nausea/vomiting or psychomimetic reactions. Conclusions: Propofol‐ketamine combination provided better quality of sedation with lesser complications than propofol alone and thus can be a good option for sedation during spinal anesthesia in children.     

C‐type natriuretic peptide slows down wound healing but promotes angiogenesis in SKH1‐hr hairless mice

C‐type natriuretic peptide (CNP) is known to increase growth rate of endothelial cells in vitro. In addition, gene transfer of CNP into ischaemic muscle was shown to induce angiogenesis. So far, no study has addressed the effect of CNP on dermal wound healing. The ear wound model in mice was used in this study. The first group was treated with dsRed‐CNP plasmid, whereas the second group was transfected with the empty dsRed‐sine plasmid, lacking sequence coding for CNP. The third group was sham operated and treated with saline to serve as second control. Wound size was measured on days 0, 1, 3, 5, 7, 9, 11 and 14. On days 7 and 14 capillary density was analysed. Wound closure rate was significantly reduced in mice treated with CNP [dsRed‐CNP 73·3 ± 3·2% versus dsRed‐sine 94·5 ± 2·4% versus saline 92·1 ± 2·4%, n = 8 per group, analysis of variance (ANOVA) P < 0·001] at day 7 postop. Capillary density was found to be significantly higher in CNP‐treated mice (dsRed‐CNP 18·7 ± 3·9 versus dsRed‐sine 12·3 ± 2·7 versus control 10·1 ± 4·7, CD31⁺ capillaries per microscope field, ANOVA P = 0·018) at day 14 postoperative. CNP significantly reduces wound closure rate in hairless mice but promotes the development of new blood vessels. A possible explanation is the dual effect of CNP, inhibiting growth of fibromyoblasts but stimulating growth of endothelial cells. Thus, CNP may serve as a therapeutic approach to diseases caused by hyperfibrosis.     

Influence of external cardiac pacing on cerebral oxygenation measured by near‐infrared spectroscopy in children after cardiac surgery

Background: The brain of children in the early period after repair of congenital heart defects with cardiopulmonary bypass (CPB) may be more vulnerable to hemodynamic changes because of impaired cerebral autoregulation. During postoperative testing of the external temporary safety pacer, we performed desynchronizing ventricular pacing (VVI) while monitoring cerebral oxygenation using near‐infrared spectroscopy (NIRS). Methods: We prospectively investigated 11 children (6 girls, 5 boys). Mean age was 6.1 months (±3.8 months) and mean weight: 5.3 kg (±1.5 kg). We performed measurements at four study steps: baseline I, VVI pacing, baseline II and atrial pacing (AOO) to exclude effects of higher heart rate. We continuously measured the effects on hemodynamic and respiratory parameters as well as on cerebral tissue oxygenation index (TOI). Hemoglobin difference (HbD) was calculated as a parameter for cerebral blood flow (CBF). Results: Ventricular pacing leads to a significant decrease in arterial blood pressure and central venous saturation accompanied by an immediate and significant decrease in TOI (63.3% ± 7.6% to 61.5% ± 8.4% [P < 0.05]) and HbD (0.51 ± 1.8 μmol·l⁻¹ to −2.9 ± 4.7 μmol·l⁻¹ [P < 0.05]). Conclusion: Cardiac desynchronization after CPB seems to reduce CBF and cerebral oxygenation in children.