Prolonged mild hypothermia after experimental hypothermic circulatory arrest in a chronic porcine model

Objectives: We sought to evaluate the potential efficacy of prolonged mild hypothermia after hypothermic circulatory arrest. Methods: Twenty pigs, after a 75-minute period of hypothermic circulatory arrest, were randomly assigned to be rewarmed to 37°C (normothermia group) or to 32°C and kept at that temperature for 14 hours from the start of rewarming (hypothermia group). Results: The 7-day survival was 30% in the hypothermia group and 70% in the normothermia group (P = .08). The hypothermia group had poorer postoperative behavioral scores than the normothermia group. Prolonged hypothermia was associated with lower oxygen extraction and consumption rates and higher mixed venous oxygen saturation levels during the first hours after hypothermic circulatory arrest. Decreased cardiac index, lower pH, and higher partial pressure of carbon dioxide were observed in the hypothermia group. There was a trend for beneficial effect of prolonged hypothermia in terms of lower brain lactate levels until the 4-hour interval and of intracranial pressure until the 10-hour interval. Postoperatively, total leukocyte and neutrophil counts were lower, and creatine kinase BB was significantly increased in the hypothermia group. At extubation, the hypothermia group had higher oxygen extraction rates and lower brain tissue oxygen tension. Conclusions: A 14-hour period of mild hypothermia after 75-minute hypothermic circulatory arrest seems to be associated with poor outcome. However, the results of this study suggest that mild hypothermia may preserve its efficacy when it is used for no longer than 4 hours, but the potentials of a shorter period of postoperative mild hypothermia still require further investigation.     

Potential neuroprotective benefits of erythropoietin during experimental hypothermic circulatory arrest

Objective: Recent studies have shown that erythropoietin protects neurons from glutamate toxicity and ischemia. This study was performed to evaluate the potential neuroprotective effect of erythropoietin during experimental hypothermic circulatory arrest. Methods: Twenty pigs were randomized to receive intravenously either 500 IU/kg recombinant human erythropoietin or saline before a 75-minute period of hypothermic circulatory arrest at an intracerebral temperature of 18°C. Results: After the administration of erythropoietin, its concentration in the cerebrospinal fluid increased 4.5-fold 8 hours after the start of rewarming, whereas it did not increase in control animals. The 7-day survival rate was 60% in the erythropoietin group and 70% in the control group (P = 1.0). No significant differences were observed between the study groups in terms of electroencephalography, behavioral score, and histopathologic score. The erythropoietin group had higher vascular resistance and mean arterial pressure values, lower intracerebral concentrations of glutamate and glycerol, higher brain tissue oxygen tension, and lower apoptotic index. Conclusions: Administration of 500 IU/kg erythropoietin intravenously before hypothermic circulatory arrest was followed by an increased erythropoietin concentration in the cerebrospinal fluid. Although previous studies have demonstrated neuroprotective effects of erythropoietin during brain ischemia, the present study, using a chronic porcine model, failed to show any significant benefit after administration of erythropoietin in terms of mortality or brain histopathology. Lower intracerebral concentrations of glutamate and glycerol, higher brain tissue oxygen tension, and lower apoptotic index observed in the erythropoietin group, however, suggest that a distinct neuroprotective effect of erythropoietin might be achieved at different dosages and timing of administration.     

Trasylol (aprotinin) decreases kidney Interleukin-1beta (IL-1beta) and IL-6 levels following renal ischemia and reperfusion injury

Introduction. Acute renal failure (ARF) may be an ominous complication of circulatory arrest in cardiac surgical patients. Aprotinin is used as a therapeutic adjunct to preserving hemostasis by inhibiting protease-mediated fibrinolysis. Aprotinin has been shown to possess anti-inflammatory properties, which may be renal protective. However, it is unknown whether aprotinin decreases renal proinflammatory cytokine production following I/R. Indeed, other agents which have reduced renal IL-1beta and IL-6 have protected renal function in this setting. We hypothesized that aprotinin would decrease renal IL-1beta and IL-6 production following I/R. Methods. Adult male rats were subjected to unilateral I/R with varying lengths of both ischemia and reperfusion, with and without clinically relevant dosing and administration of aprotinin prior to the insult (clinically aprotinin is given prior to circulatory arrest). At various time points, the kidneys were harvested and the tissue homogenates were assayed for IL-1beta and IL-6 (ELISA). All experiments were approved by the Indiana University Animal Care and Use Committee (IACUC). Results. One-hour ischemia and 2 h of reperfusion significantly increased renal tissue IL-1beta and IL-6 levels (P < 0.05 versus sham, ANOVA with Bonferroni/Dunn). Aprotinin significantly (P < 0.05) decreased renal IL-1beta and IL-6 levels at this time point. Aprotinin also significantly decreased renal IL-1beta at the 1 h ischemia/4 h reperfusion time point. At no point did aprotinin increase production of either cytokine. Conclusions. Aprotinin decreases renal proinflammatory cytokine production following I/R. Further study will be needed to determine if aprotinin decreases renal tubular apoptosis and acute renal failure following such conditions. If so, aprotinin may be useful as an adjunct to preserving renal function following diverse planned ischemic events.     

Neonates with congenital diaphragmatic hernia have smaller neck veins than other neonates-An alternative route for ECMO cannulation

Background/Purpose: The aim of this study was to compare the size of the right internal jugular vein between neonates with congenital diaphragmatic hernia (CDH) who need extracorporeal membrane oxygenation (ECMO) and non-CDH neonates. The purpose also was to describe a method for cannulation of the right brachiocephalic vein if the internal jugular vein was too small for ECMO cannulation. Methods: Birth weight and size of the right internal jugular vein were compared between CDH and non-CDH neonates subjected to ECMO treatment. A corrected venous size was calculated, estimating the venous size if the patient's birth weight was 3,000 g. Results: The mean birth weight of the CDH patients (3,214 g) was lower than that of the non-CDH patients (3,497 g; P [lt ] .04). The mean venous size of the CDH patients (12.1 Charierre [Ch]) was significantly smaller (P [Lt ] .001) than that of non CDH patients (13.6 Ch). The corrected venous size also was significantly (P [lt ] .001) smaller among CDH patients. Conclusions: Severely affected neonates with CDH have significantly smaller right internal jugular veins than other neonates. If the patient needs ECMO and if the internal jugular vein is too small for cannulation, the right brachiocephalic vein can be successfully cannulated from the neck instead. J Pediatr Surg 37:906-908.     

Profound hypothermia preserves neurons and astrocytes, and protects cognitive functions in a swine model of lethal hemorrhage

Lethal injuries can be repaired under asanguineous hypothermic arrest (suspended animation) with excellent survival. This experiment was designed to test the impact of different cooling rates on CNS cellular damage and on cognitive functions in a swine model. Methods. Uncontrolled hemorrhage was induced in 32 female swine (80-120 lbs) by creating an iliac artery and vein injury, followed 30 min later (simulating transport time) by laceration of the thoracic aorta. Through a thoracotomy approach, a double lumen catheter was placed in the aorta and hyperkalemic organ preservation solution was infused on cardiopulmonary bypass (CPB). Experimental groups were normothermic controls (no cooling, NC), or hypothermia induced at a rate of 0.5°C/min (slow, SC), 1°C/min (medium, MC), or 2°C/min (fast, FC). Profound hypothermia (10°C) was maintained for 60 min for repair of vascular injuries. Hyperkalemia was then reversed and blood was infused for resuscitation during rewarming (0.5°C/min). Circulating levels of neuron-specific enolase (NSE) and S 100-beta (S-100) were serially measured as markers of damage to neurons and astrocytes, respectively. Surviving animals were observed for 6 weeks and monitored for neurologic deficits. Cognitive function (learning) was evaluated based on the concept of operant conditioning. Quantitative immunohistochemical (IHC) examination was performed to measure neuronal damage and astrogliosis (astrocyte hyperplasia/ hypertrophy) in different areas of the brains. Results. The 6-week survival rates were 0% (NC), 37.5% (SC), 62.5% (MC), and 87.5% (FC) respectively (P < 0.05, NC versus MC and FC). Normothermia resulted in brain death, whereas all of the surviving hypothermic animals were neurologically intact and showed normal learning capacity. The NSE increased after shock and S-100 levels increased after CPB, independent of the temperature modulation. At 6 weeks, brains displayed no neuronal damage or astrogliosis. Conclusion. Profound hypothermia can preserve neuronal viability during prolonged periods of cerebral hypoxia. This approach is associated with excellent cognitive and neurologic outcome.     

Effects of partial liquid ventilation on cerebral blood flow and cerebral metabolism in neonatal lambs

Background/Purpose: Liquid ventilation is a promising therapy for respiratory failure. The effects of perfluorochemical on cardiac output have not been well described. The purpose of this study was to compare cerebral blood flow (Q_CAROTID) and cerebral metabolic rates (CMR) during conventional ventilation (CV) and partial liquid ventilation (PLV). Methods: Five 2-week-old lambs underwent tracheostomy and central venous, aortic, and postcerebral venous catheter placement. Doppler flow probes were placed around the common ovine trunk, and the lambs underwent CV for 1 hour. Ventilation was adjusted to maintain physiologic blood gases. Pre- and postcerebral blood gas, glucose, and lactate samples were obtained every 15 minutes. Perfluorodecalin then was instilled endotracheally. The lambs underwent 1 hour of PLV with similar sampling. Data were analyzed using the Wilcoxon matched pairs test, significance at P [le ] .05. Results: The authors observed no difference in mean Q_CAROTID or carotid vascular resistance between CV and PLV (P = .35 and .34, respectively). The CMR of oxygen, glucose, and lactate were calculated using the Fick principle. CMR was unchanged between modes (P = .5). Conclusions: PLV did not adversely alter Q_CAROTID or CMR in lambs, implying that this mode of ventilation should be safe in neonatal patients at risk for neurologic injury. J Pediatr Surg 37:840-844.     

A possible mechanism for prevention of intestinal programmed cell death after ischemia-reperfusion injury by hepatocyte growth factor pretreatment

Background/Purpose: Intestinal ischemia-reperfusion (IR) injury produces necrosis and apoptosis resulting in tissue loss. The authors have observed previously that pretreatment with hepatocyte growth factor (HGF) attenuates enterocyte apoptosis after IR. This study investigated the effects of HGF on tissue levels of caspase-8, an apoptosis initiator, and caspase-3, an apoptosis effector, in intestinal mucosa after IR. Methods: Thirty rats underwent placement of jugular venous catheters connected to osmotic pumps; 15 rats received vehicle, and 15 rats received HGF (150 [mu ]g/kg/d). After a 48-hour infusion, 5 rats from each group underwent either 35 minutes of superior mesenteric artery occlusion alone, or ischemia followed by 2 or 6 hours of reperfusion. Mucosal protein was analyzed for caspase-8 and caspase-3 activity. DNA fragmentation was used to measure the presence of apoptosis. Statistical significance was determined using analysis of variance. Results: After 6 hours of reperfusion, caspase-3 activity was increased significantly in control animals (P [lt ] .05). In HGF-pretreated animals, caspase-8 and caspase-3 activities were significantly reduced at 6 hours compared with control animals (P [lt ] .05). Conclusion: By preventing the activation of enterocyte caspase enzymes, and, thus, reducing apoptosis, HGF may enhance preservation of the intestine after IR injury.     

Mast cell activation and arterial hypotension during proximal aortic repair requiring hypothermic circulatory arrest

Objective

Aortic surgeries requiring hypothermic circulatory arrest evoke systemic inflammatory responses that often manifest as vasoplegia and hypotension. Because mast cells can rapidly release vasoactive and proinflammatory effectors, we investigated their role in intraoperative hypotension.

Elevated serum levels of S-100 after deep hypothermic arrest correlate with duration of circulatory arrest

Objective.

Cerebral damage is a major problem after reconstructive surgery of the aortic arch and the descending aorta. Current protective strategies, including deep hypothermia and retrograde cerebral perfusion, are used to prolong the tolerated duration of circulatory arrest, and the latter may also decrease the possibility of air/particle embolization. The aim of the current study was to investigate whether the neurochemical marker S-100 is related to the duration of circulatory arrest, when the influence of embolic injury has been minimized by the use of retrograde cerebral perfusion during the last part of circulatory arrest.

Methods.

Arterial serum levels of S-100 were followed before, during and after reconstructive surgery of the thoracic aorta during deep hypothermic arrest in ten adults. Retrograde cerebral blood perfusion was used during the latter part of the arrest period in eight of the ten patients. Neurologic status was followed daily.

Results.

All patients survived the operation. The median (range) duration of cardiopulmonary bypass (CPB) was 184.5 (121 – 386) min. The median duration of circulatory arrest and retrograde cerebral perfusion was 50 (3 – 118) min and 16 (0 – 84) min, respectively. S-100 increased from 0.10 (0.02 – 0.18) g/l preoperatively to 2.37 (0.64 – 10.80) g/l after CPB (P<0.01), followed by a decrease to 0.79 (0.21 – 2.64) g/l on the first postoperative day (P<0.01). The duration of circulatory arrest correlated with S-100 levels after CPB (r_S=0.71, P<0.05) and even better with the S-100 levels on the first postoperative day (r_S=0.83, P<0.01). However, there was no significant correlation between duration of arrest and duration of CPB. The duration of circulatory arrest without retrograde cerebral perfusion correlated well with S-100 levels on the first postoperative day (r_S=0.88, P<0.01), but not significantly with S-100 levels after CPB.

Conclusions.

S-100 levels after aortic surgery with deep hypothermic arrest correlate with the duration of circulatory arrest, indicating that the duration of circulatory arrest is damaging to the brain despite the use of deep hypothermia and partial retrograde cerebral perfusion. The highest correlation between S-100 and duration of arrest was seen on the first postoperative day. S-100 appears to perform well under clinical circumstances as a sensitive and discriminative marker for neuronal injury.     

Apigenin enhances gemcitabine-induced pancreatic cancer cell apoptosis

Body. Pancreatic adenocarcinoma is only marginally responsive to its first-line chemotherapeutic agent, gemcitabine. Apigenin, a naturally occurring flavanoid, has been shown to inhibit growth in some cancer cell lines but has not been studied in pancreatic cancer. We hypothesized that apigenin would inhibit growth and enhance gemcitabine’s effect on pancreatic cancer cells. Methods. Four human pancreatic cancer cell lines (AsPC-1, CD18, MiaPaCa2, and S2013) were treated with varying concentrations (6.25-100 μM) of apigenin alone and in combination with gemcitabine (100 μM). Cells were analyzed at different time points (24-96 h). Proliferation was measured by ³H-thymidine incorporation and cell counting. Cell-cycle analysis and apoptosis was determined by flow cytometry with propidium iodide DNA staining and annexin-V binding. Cell-cycle-associated proteins were investigated by Western blotting. Analysis of variance was used to determine if there were significant differences among the means. Results. Apigenin caused both time- and concentration-dependent inhibition of DNA synthesis (55% decrease in 24 h, P < 0.001) and cell proliferation (81.4% decrease in 72 h, P < 0.001) of all four pancreatic cancer cell lines. Apigenin induced G2/M phase cell-cycle arrest (control 12.88% versus treated 21.54%, P < 0.002). Apigenin reduced levels of cyclin A, B, cdc2 phosphatase, and cdc25 (proteins required for G2/M transition). With gemcitabine, apigenin increased the number of apoptotic cells more than either agent alone (combination 32.5% versus control 5.0%, P < 0.001; versus apigenin 11.7%, P < 0.01; versus gemcitabine 15.3%, P < 0.05). Conclusions. Apigenin inhibits growth of pancreatic cancer cells through suppression of cyclin B-associated cdc2 activity and G2/M arrest. Even greater effect was seen in combination with gemcitabine. Apigenin enhances gemcitabine-induced apoptosis in pancreatic cancer cells and appears promising in combination as a chemotherapeutic agent.     

Connective tissue growth factor expression is decreased in acute ascending aortic dissections and increased in degenerative ascending aortic aneurysms

Purpose. Both aortic aneurysms and aortic dissections exhibit abnormal extracellular matrix properties. Connective tissue growth factor (CTGF) can induce connective tissue cell proliferation and extracellular matrix synthesis. The role of CTGF in thoracic aortic disease has never been investigated. We sought to compare the expression of CTGF in degenerative ascending aortic aneurysms and ascending aortic dissection. Methods. Intraoperative samples of ascending aorta were obtained from 47 patients: 16 patients had ascending aortic aneurysms with medial degeneration, 10 had acute aortic dissection, 9 had aneurysms due to chronic dissection. Control ascending aorta was obtained from organ donors and heart transplant recipients (n = 10). Patients with Marfan syndrome were excluded from this study. CTGF mRNA expression within aortic wall was semiquantitatively determined by real-time RT-PCR using GAPDH as the internal standard. Results. There was a significant increase in CTGF mRNA in degenerative aneurysms compared to control tissue (P = 0.04). Conversely, patients with acute dissection had decreased CTGF mRNA expression compared with nondissection aneurysms (P = 0.019) and controls (P = 0.06). The increase in CTGF expression in chronic dissections compared to acute dissections approached statistical significance (P = 0.075). Conclusions. The altered tissue levels of CTGF in aneurysms and dissections suggest possibly different molecular pathology in these aortic disorders. Further investigation regarding the role of CTGF in thoracic aortic disease is warranted.     

Vein wall remodeling after deep vein thrombosis involves matrix metalloproteinases

Background. Deep venous thrombosis (DVT) confers vein wall damage associated with fibrosis and extracellular matrix turnover, mediated by proteases. This study investigated the molecular expression of proteases and collagen involved in early vein wall remodeling. Methods. In the mouse, DVT was produced by ligation of the infrarenal inferior vena cava (IVC), or sham operation, and tissue harvested at 4, 8, and 12 days. The vein wall tissue was processed for real-time PCR (ratio of gene to b-actin), Western immunoblotting, and gelatin zymography. ANOVA was used for multiple comparisons and a P < 0.05 was significant. All N = 6-8. Results. Thrombus resolution was documented by a 1.6-fold decrease in the thrombosed IVC weight:length ratio over 12 days (P = 0.007). MMP-2 gene expression was 23-fold greater at 12 days as compared to sham or the 4-day time point (P < 0.05). Total MMP-2 activity by zymography was significantly elevated at 12 days as compared with sham (P = 0.047). MMP-7 expression peaked at 4 days (76-fold; P = 0.003) but approached baseline thereafter. MMP-9 expression was 19-27 higher at days 4 and 8, respectively, both relative to shams (P < 0.05), but no difference in activity was found. MMP-14 expression was 2- to 3.6-fold greater at day 12 compared to earlier time points and shams (P < 0.001), but no difference in protein levels was found. Plasminogen activator inhibitor was increased at 4 days relative to sham, but not after 8 days. Procollagen I and III increased over time and peaked at 12 days (24-fold, 6.1-fold, respectively, P < 0.02). Conclusions. Vein wall remodeling after DVT is associated with persistent procollagen up regulation and primarily MMP-2 expression and activity, whereas other proteases may be less important.     

Amniotic fluid beta-endorphin: a prognostic marker for gastroschisis?

Purpose: The aim of this work was to study amniotic fluid [beta ]-endorphin as a potential predictor for postnatal morbidity in gastroschisis. Methods: Beta-endorphin was assayed in 43 amniotic fluid samples from 13 pregnant women with fetal gastroschisis undergoing diagnostic amniocentesis or therapeutic amnioinfusion and compared with 33 controls. Within the gastroschisis group, the authors investigated the relationship between postnatal morbidity and the peak value of amniotic fluid [beta ]-endorphin (AFBE). Results: Ten AFBE values in 6 cases of gastroschisis were above the upper limit of the 95% confidence interval derived from controls. Postnatal morbidity was significantly higher when peak AFBE exceeded 10 [mu ]g/L (n = 4 pregnancies) compared with below 5 [mu ]g/L (n = 9 pregnancies), as shown by mean duration of mechanical ventilation (15.2 v 3 days; P = .01), of parenteral feeding (77 v. 18.7 days; P = .04), and of hospitalization (84 v 32.2 days; P = .04). There was no statistically significant association between postnatal morbidity markers and prenatal dilation of fetal bowel. Conclusions: The most severe cases of gastroschisis are associated with high levels of AFBE. The authors speculate that this fetal hormonal response could result from stress or pain caused by prenatal bowel damage.     

Extracorporeal membrane oxygenation in piglets using a polymerized bovine hemoglobin-based oxygen-carrying solution (HBOC-201)

Purpose: The purpose of this study was to determine if the polymerized bovine hemoglobin-based oxygen-carrying solution HBOC-201 is an acceptable substitute for blood in a healthy porcine, extracorporeal membrane oxygenation (ECMO) model. Methods: Ten piglets (15 to 25 kg) were placed on venoarterial ECMO. Four animals received blood-primed ECMO, and 6 animals received HBOC-201[ndash ]primed ECMO. Hemodynamic variables, urine output, blood gas analyses, complete blood counts, and lactate levels were followed for 6 hours. Data were analyzed using a nonparametric sign test and repeated measures analysis of variance (ANOVA). Results: All animals survived the 6-hour ECMO procedure. Heart rate, mean arterial pressure, urine output, and serum lactate levels were not significantly different between groups. Postpriming volume was 176 [plusmn] 156 mL in the blood group. None of the animals in the HBOC-201 group required additional volume to maintain target flow during ECMO (P [lt ] .05). Arterial pH, pO₂, and oxygen content between groups were not significantly different. Hematocrit for the HBOC-201 group was significantly (P [lt ] .05) lower than the blood group. Conclusions: HBOC-201[ndash ]primed ECMO in a healthy porcine model showed similar hemodynamics and equivalent oxygen carrying capacity to blood-primed ECMO. Postpriming volume requirement was decreased significantly in the HBOC group. ECMO using HBOC-201 instead of blood appears promising and warrants further investigation. J Pediatr Surg 37:1387-1392.     

Comparison of delayed complications of central venous catheters placed surgically or radiologically in pediatric oncology patients

Purpose: Pediatric central venous catheters (CVCs) traditionally have been placed surgically, guided by anatomic landmarks. Increasingly, interventional radiology services are inserting CVCs using ultrasound image guidance. This study compares the frequency of delayed complications in CVCs placed surgically or radiologically in a pediatric oncology population. Methods: Data on CVCs placed in one academic institution over 10 years were collected and analyzed retrospectively. Main outcomes assessed were infectious complications, mechanical complications, and premature catheter removal. Results: Ninety-eight CVCs[mdash ]comprising 52 external tunneled catheters (ETCs) and 46 subcutaneous ports[mdash ]were assessed in 67 patients. Median patient age was 6.1 years for children with external catheters and 7.8 years for those with ports. Both infectious and mechanical complications were significantly more common among surgically placed ETCs than those placed radiologically (P [lt ] .05). Complications per 1,000 catheter days and premature removal showed a trend toward greater frequency among surgical ETCs, although this did not reach statistical significance. No consistent trends were seen in complications among ports. Conclusions: Pediatric patients with CVCs, especially those with external catheters, experience frequent delayed complications. Patients with radiologically inserted ETCs may encounter fewer complications than those with surgically placed ones. This corroborates previous reports in the literature suggesting image-guided CVC placement as a preferable alternative to traditional techniques. J Pediatr Surg 38:788-792. [copy ] 2003 Elsevier Inc. All rights reserved.     

Body temperature and heat production in suckling rat endotoxaemia: beneficial effects of glutamine

Background/Purpose: Sepsis is an important cause of neonatal mortality. The aim of the study was to investigate the metabolism of endotoxic neonatal rats and the potential beneficial effect of glutamine. Methods: Suckling rats received intraperitoneal saline (control; C), endotoxin (300 [mu ]g/g LPS; E), saline+glutamine (2 mmol/g; CG), endotoxin+glutamine (EG), saline+leucine (2 mmol/g; CL) or endotoxin+leucine (EL). Sepsis score (0-8) and rectal temperature were monitored. Hypothermia was defined as rectal temperature less than 32[deg ]C. Oxygen consumption (VO₂, mL/kg/h), a determinant of heat production, was measured by indirect calorimetry. Data (mean [plusmn] SEM) were compared by analysis of variance (ANOVA), paired t test or Fisher's Exact test. Results: Endotoxic (E) rats had significantly lower VO₂ than C rats from 90 minutes postinjection to the end of the experiment, 210 minutes (VO₂ from 150 to 210 minutes: C 671 [plusmn] 45; E 429 [plusmn] 36, P [lt ] .0004; n = 8; paired t test). VO₂ of CL or CG rats was elevated between 90 and 210 minutes compared with control, but significantly (P [lt ] .01) only in the L group (C 706 [plusmn] 31; CG 871 [plusmn] 63; CL 984 [plusmn] 31; n = 7-9, ANOVA). VO₂ was significantly higher (P [lt ] .05) in EG rats than E rats (E 460 [plusmn] 29; EG 654 [plusmn] 68; n = 9-10). In the EL group, VO₂ was raised but was not significantly different from E (E 460 [plusmn] 29; EL 637 [plusmn] 52; n = 8-10). EG rats were significantly less hypothermic between 90 and 210 minutes (58 of 132 measurements) compared with E (95 of 147; P = .0007, Fisher's Exact test), whereas the EL group were similarly hypothermic (74 of 120) to E (P = .7). Sepsis score was significantly lower in the EG group than both E and EL groups (E 4.9 [plusmn] 0.3; EG 3.6 [plusmn] 0.3; EL 5.0 [plusmn] 0.3; n = 40; P [lt ] .01; ANOVA). Conclusions: Neonatal endotoxaemia lowers VO₂, heat production, and body temperature. Glutamine and leucine both cause nutrient-induced thermogenesis in control animals and restore VO₂ of endotoxic animals. Glutamine additionally increases rectal temperature, reduces incidence of hypothermia, and improves clinical signs of endotoxic rats. This suggests that glutamine may be beneficial for nutrition in neonatal sepsis. J Pediatr Surg 38:37-44.     

Innovative minimally invasive pediatric surgery is of therapeutic value for splenic injury

Background/Purpose: Until now, minimally invasive surgery (MIS) has not had any therapeutic status for operable splenic trauma, because reliable sealing of larger defects is not possible with general techniques. Methods: Fleece-bound sealing allows rapid, large-area sealing of erosions and defects, so that with the aid of an MIS applicator system (AMISA), this method of tissue management can be transferred to MIS. Results: An in vitro evaluation showed that liquid fibrin sealing (FS) exhibits incomplete selective leak closure and low adhesive strength (4.1 hPa) and is not suitable for challenging surfaces. Fleece-bound sealing (ready-to-use v. prepare-to-use) showed reliable sealing and higher adhesive strength for collagen fleeces that are ready coated with fibrinogen-based sealant (TachoComb H; Nycomed, Linz, Austria) compared with various carrier systems that had to be impregnated on the spot (prepare-to-use; 50.2 v 23 hPa; P [lt ] .0001). Between October 1993 and October 2001, 19 of 87 children with splenic rupture were treated with the AMISA system (AMISA + TachoComb H) (21.8%), and 3 of these children had multiple trauma. The operation was indicated because of circulatory instability despite adequate volume replacement therapy. Splenic repair always was possible with the AMISA system, a changeover and splenectomy was not necessary, and the postoperative course was complication free. The mean stay in the hospital was 9.2 days. Conclusions: The AMISA system efficiently expands the indications for emergency laparoscopy and can be used successfully in emergency laparoscopy for splenic rupture management. J Pediatr Surg 37:1146-1150.     

Uptime as a measure of recovery in children postappendectomy

Purpose: The aim of this study was to objectively measure recovery time after open and laparoscopic appendectomy using an activity monitor (PAL 1).Methods: The PAL 1 records the amount of time that the subject is upright (uptime). Children wore the PAL 1 for 10 days continuously, beginning within the first 48 hours postoperatively.Results: Uptime data were collected for 5 or more days for 42 children (open, n = 16; laparoscopic, n = 26). All children had low levels of uptime in the initial postoperative period. There was weak evidence of a quicker recovery rate for children in the laparoscopic group (P = .09). The difference in mean uptime between groups was of statistical significance by day 7 postoperatively with children in the laparoscopic group having a higher mean uptime than those in the open group (difference of 0.7 hours; 95% confidence intervals 0.0 to 1.4 hours in a 24-hour period).Conclusions: The results of this study show that recovery postappendectomy can be quantified by the measurement of uptime and that children undergoing a laparoscopic procedure may recover marginally more quickly than those undergoing an open procedure.