Immediate and 5-year outcome after coronary artery bypass surgery in very high risk patients (additive EuroSCORE ≥ 10).

AIM: We have evaluated the outcome after coronary artery bypass surgery in very high risk patients (additive EuroSCORE ≥ 10). The impact of beating heart coronary artery bypass surgery (BHCAB) on their outcome has been evaluated. METHODS: Retrospective study including 160 consecutive patients with additive EuroSCORE ≥ 10. RESULTS: . The overall survival rates at 30-day, 1-year, 3-year and 5-year were 83.8%, 76.0%, 72.4% and 66.8%, respectively. Baseline cardiac index (O.R. 0.20, 95%C.I. 0.08-0.53), preoperative inotropic support (O.R. 4.55, 95%C.I. 1.41-14.73) and preoperative resuscitation (O.R. 3.937, 95%C.I. 1.02-15.26) were independent predictors of 30-day mortality. Baseline cardiac index (R.R. 0.48, 95%C.I. 0.28-0.85), left ventricular ejection fraction (P=0.032), preoperative use of intraaortic balloon pump (R.R. 3.22, 95% C.I. 1.50-6.93), preoperative tracheal intubation (R.R. 3.44, 95%C.I. 1.37-8.68) and creatinine (R.R. 1.004, 95%C.I. 1.00-1.01) were independent predictors of late death. OPCAB/BHCAB was associated with somewhat lower 30-day mortality rate (16.2% vs. 18.0%, P=0.73), stroke (2.0% vs. 4.9%, P=0.37), red blood cells transfusion (3.4 vs. 5.4 units, P=0.004) and combined adverse outcome (43.4% vs. 50.8%, P=0.42). OPCAB/BHCAB surgeons compared with surgeons with a prevalent conventional approach achieved slightly better the 30-day mortality rate (16.7% vs. 27.9%, P=0.15) and stroke rate (2.8% vs. 4.7%, P=0.60) and 5-year survival rate (65.3% vs. 57.4%, P=0.35). CONCLUSION: Despite their poor immediate postoperative outcome, 5-year survival of these high risk patients is satisfactory and supports efforts in the treatment of this very high risk population. A more confident approach toward OPCAB/BHCAB is also suggested in these patients.

Changing incidence and outcome of infants with respiratory distress syndrome in the 1990s: a population-based survey.

AIM: To evaluate the trends in the incidence, clinical course and outcome of respiratory distress syndrome (RDS) in the newborn in the Oulu University Hospital region in northern Finland. METHODS: In the population of 58 990 infants, the incidence rates of RDS specific to gestational age and birthweight in two consecutive periods, 1990-95 and 1996-99, were calculated. Clinical course and other neonatal morbidities were reported. All surviving infants were followed up until 1 y of corrected age. RESULTS: The overall incidence of RDS did not change significantly (8.7/1000 livebirths in 1990-95 vs 7.6 in 1996-99; p = 0.15), but the gestational age-adjusted incidence decreased between the two consecutive periods (p = 0.005). The frequency of infants with gestational age below 28 wk tended to increase towards the late 1990s, while their RDS incidence remained unchanged. RDS-related neonatal mortality decreased in parallel with neonatal mortality, accounting for 15% of all neonatal deaths. The duration of oxygen therapy shortened (8.0 vs 5.5 d) and the incidence of pneumothorax decreased (9.7 vs 4.1%), whereas the rate of chronic lung disease at 36 wk of postconceptional age (16.4 vs 16.7%) and at 1 y of corrected age (9.2 vs 8.2%) remained unchanged, as did also associated neurosensory morbidity (8.8 vs 9.5%). CONCLUSION: During the 1990s, the incidence of RDS shifted towards more immature infants and the gestational-age specific incidence decreased. The course of the disease shortened and acute complications decreased. The frequency of chronic pulmonary sequelae (and associated neurosensory morbidity) at the age of 1 y did not change significantly.

Nitric oxide treatment and acute pulmonary inflammatory response in very premature infants with intractable respiratory failure shortly after birth.

AIM: Premature infants with respiratory failure and early-onset pneumonia have low inducible nitric oxide synthase (NOS2) and no evidence of nitric oxide (NO) toxicity. However, inhalation of NO may not be indicated in sepsis because excessive NO generation has been reported. This prospective study was designed to test the hypothesis that inhaled NO is effective in a select group of small premature infants and that the responsiveness to NO is associated with low NOS2 enzyme. METHODS: 246 very low birthweight infants (birthweight <1500 g, VLBW) were screened for severe, intractable respiratory failure (oxygenation index >40, arterial-alveolar ratio for oxygen tension <0.10) that does not respond to two doses of surfactant within 5 h from birth. Infants with severe cardiac failure or a bleeding disorder were excluded. Five of the nine eligible cases received inhaled NO. They all had prolonged rupture of foetal membranes, early-onset pneumonia and persistent pulmonary hypertension. RESULTS: All five responded strikingly, survived and appeared normal in follow-up. Airway specimens during the first day of life revealed very low NOS2, interleukin-1beta and surfactant protein A, compared with VLBW infants who had no acute infection despite histological chorioamnionitis. In early-onset pneumonia, NOS2 and other inflammatory mediators increased first during the recovery 1-2 d after birth. CONCLUSION: VLBW infants with progressive respiratory failure and infection at birth have deficient pulmonary NOS2 and cytokine response. After surfactant therapy, these infants responded strikingly to inhaled NO. An acute pulmonary inflammatory response may contribute to respiratory adaptation in early-onset pneumonia.

A national two year follow up study of extremely low birthweight infants born in 1996-1997.

OBJECTIVE: To study neurodevelopmental outcome in a two year cohort of extremely low birthweight (ELBW) infants at 18 months corrected age, to compare the development of the ELBW infant subcohort with that of control children, and to find risk factors associated with unfavourable outcome. STUDY DESIGN: All 211 surviving ELBW infants (birth weight < 1000 g) born in Finland in 1996-1997 were included in a national survey. The ELBW infants (n = 78) who were born and followed in Helsinki University Hospital belonged to a regional subcohort and were compared with a control group of 75 full term infants. A national follow up programme included neurological, speech, vision, and hearing assessments at 18 months of corrected age. Bayley infant scale assessment was performed on the subcohort and their controls at 24 months of age. Risk factors for unfavourable outcome were estimated using logistic and linear regression models. RESULTS: The prevalence of cerebral palsy was 11%, of all motor impairments 24%, of ophthalmic abnormalities 23%, and of speech delay 42%. No impairment was found in 42% of children, and 18% were classified as severely impaired. The prevalence of ophthalmic abnormalities decreased with increasing birth weight and gestational age, but the prevalence of other impairments did not. In the subcohort, a positive correlation was found between the date of birth and Bayley scores. CONCLUSION: Ophthalmic abnormalities decreased with increasing birth weight and gestational age, but no other outcome differences were found between birthweight groups or in surviving ELBW infants born at 22-26 weeks gestation. The prognosis in the regional subcohort seemed to improve during the short study period, but this needs to be confirmed.

Exhaled and nasal nitric oxide in mechanically ventilated preterm and term newborns.

AIM: Nitric oxide (NO) is an important mediator required for neonatal pulmonary circulatory adaptation and for pulmonary defence. Both deficient and excessive NO production have been proposed to play a role in neonatal lung disease. This study aimed to establish a method that allows direct measurement of exhaled and nasal NO concentrations in newborn infants who require intubation and ventilation. METHODS: A rapid-response chemiluminescence NO analyser was used. Gas was sampled from the endotracheal intubation tube, and tidal volumes and flow rates were measured. The nasal NO was sampled from the non-intubated nostril. The accuracy of the method was validated using a lung model. NO levels from six preterm and six term/near-term newborns were studied. Measurements were performed on a daily basis during the first week. RESULTS: An expiration >0.2 s in duration with a flow rate >1.7 ml s(-1) could be accurately analysed for the presence of >1 parts per billion of NO. The very preterm infants with neonatal lung disease had a different postnatal NO output pattern from the lower and upper airways compared with the ventilated term/near-term infants. CONCLUSION: A novel method for measurement of exhaled NO of an intubated newborn is presented. The possible association of exhaled NO concentration with the development of chronic lung disease remains to be studied.

Apoptotic activity is increased in brain cortex infarct after hypothermic circulatory arrest in a porcine model.

OBJECTIVE: It has been shown that apoptosis contributes to neuronal cell death after ischemia, and we evaluated the degree of apoptotic activity occurring in brain cortex of pigs after hypothermic circulatory arrest (HCA). DESIGN: Thirty-one pigs underwent 75 min of HCA at 20 degrees C. Histological examination of the brain was performed, and slides of brain cortex were evaluated for apoptotic activity by the TUNEL method. RESULTS: Ten animals died during the first postoperative day and 21 survived until the seventh postoperative day. Brain cortex infarcts were found in animals that survived 7 days and these were included in this study. The median histopathological score among animals that died on the first postoperative day was 3.0 (range, 2-4), whereas it was 4.0 (range, 2-4) among survivors (p = 0.019). The apoptotic index was particularly high in the area of the infarct, whereas only a few TUNEL-stained cells were observed in noninfarcted areas. The apoptotic index was nil in all pigs that died in the first postoperative period, whereas it was 2.0 (range, 0-6) among the animals that survived until the seventh postoperative day (p < 0.0001). CONCLUSION: The apoptotic index was significantly increased in brain cortex infarcts of animals that survived 7 days after HCA, whereas only a few apoptotic cells were observed in noninfarcted areas of these animals as well as in animals that died on the first postoperative day. Further studies are required to elucidate the timing of development of brain infarction after HCA and whether neuroprotective strategies targeting the apoptotic process may mitigate brain damage.

Determinants of mortality after hypothermic circulatory arrest in a chronic porcine model.

OBJECTIVE: Beside neurological morbidity, mortality is a relevant end-point of experimental porcine model of hypothermic circulatory arrest (HCA) and this study was conducted to identify the determinants for postoperative death. METHODS: One hundred and thirty-five pigs underwent a 75-min period of HCA at 20 degrees C to evaluate the efficacy of different methods of cerebral protection. RESULTS: Survival rate at 7-day follow-up was 52%. Lower oxygen extraction, oxygen consumption/kg, and venous lactate at the end of cooling and higher oxygen delivery rates were significantly associated with better outcome. Logistic regression showed that the oxygen consumption/kg at the end of cooling was the only predictor of mortality (P=0.046). Animals with an oxygen consumption/kg rate less than 1.43 ml/min per kg at the end of cooling had a mortality rate of 28%, whereas it was 50% among animals with an oxygen consumption/kg rate higher or equal to 1.43 ml/min per kg (P=0.020). The latter had even an increased 1-day mortality rate (40% vs. 26%) (P not significant). The mortality rate after anesthesia induction with ketamine plus 100% of oxygen was 38%, 45% after anesthesia induction with ketamine plus 35% oxygen, and 53% after anesthesia with medetomidine plus 35% oxygen (P not significant). CONCLUSIONS: Parameters of oxyhemodynamics should be monitored especially from the induction of anesthesia to the end of cooling before a 75-min period of HCA. The use of medetomidine and/or 35% of oxygen at induction of anesthesia should be avoided in favor of ketamine plus 100% of oxygen.

The N-methyl-D-aspartate antagonist memantine has no neuroprotective effect during hypothermic circulatory arrest: a study in the chronic porcine model.

BACKGROUND: Glutamate excitotoxicity has an important role in the development of brain injury after prolonged hypothermic circulatory arrest. The goal of the present study was to determine the potential efficacy of memantine, an N -methyl-D -aspartate receptor antagonist, to mitigate cerebral injury after hypothermic circulatory arrest. METHODS: Twenty pigs (23-33 kg) were randomly assigned to receive memantine (5 mg/kg) or placebo in a blinded fashion before a 75-minute period of hypothermic circulatory arrest at 20 degrees C. Hemodynamic, electroencephalographic, and metabolic monitoring were carried out. The intracerebral concentrations of glucose, lactate, glutamate, and glycerol were measured by means of enzymatic methods on a microdialysis analyzer. Daily behavioral assessment was performed until the animals died or were put to death on day 7. Histologic analysis of the brain was carried out in all animals. RESULTS: In the memantine group, 5 of 10 animals survived 7 days compared with 9 of 10 in the placebo group. The median behavioral score at day 7 was 3.5 in the memantine group and 7.5 in the placebo group (P >.2). Among the surviving animals, medians were 9.0 and 8.0 on day 7 (P >.2), respectively. The medians of recovered electroencephalographic bursts were equal in both groups. The median of total histopathologic score was 16 in the memantine group and 14 in the placebo group (P >.2). There was a negative correlation between glutamate levels and electroencephalographic burst recovery (tau = -0.377, P =.043). A positive correlation was found between the highest individual glutamate value and histopathologic score (tau = 0.336, P =.045). CONCLUSIONS: The present study demonstrates that memantine has no neuroprotective effect after hypothermic circulatory arrest in the pig. In addition, we have shown the accuracy of cerebral glutamate measurements to predict histopathologic injury after hypothermic ischemia.

A national short-term follow-Up study of extremely low birth weight infants born in Finland in 1996-1997.

OBJECTIVES: The aims of this prospective nationwide investigation were to establish the birth rate, mortality, and morbidity of extremely low birth weight (ELBW) infants in Finland in 1996-1997, and to analyze risk factors associated with poor outcome. PARTICIPANTS AND METHODS: The study population included all stillborn and live-born ELBW infants (birth weight: <1000 g; gestational age: at least 22 gestational weeks [GWs]), born in Finland between January 1, 1996 and December 31, 1997. Surviving infants were followed until discharge or to the age corresponding with 40 GWs. National ELBW infant register data with 101 prenatal and postnatal variables were used to calculate the mortality and morbidity rates. A total of 32 variables were included in risk factor analysis. The risk factors for death and intraventricular hemorrhage (IVH) of the live-born infants as well as for retinopathy of prematurity (ROP) and oxygen dependency of the surviving infants were analyzed using logistic regression models. RESULTS: A total of 529 ELBW infants (.4% of all newborn infants) were born during the 2-year study. The perinatal mortality of ELBW infants was 55% and accounted for 39% of all perinatal deaths. Of all ELBW infants, 34% were stillborn, 21% died on days 0 through 6, and 3% on days 7 though 28. Neonatal mortality was 38% and postneonatal mortality was 2%. Of the infants who were alive at the age of 4 days, 88% survived. In infants surviving >12 hours, the overall incidence of respiratory distress syndrome (RDS) was 76%; of blood culture-positive septicemia, 22%; of IVH grades II through IV, 20%; and of necrotizing enterocolitis (NEC) with bowel perforation, 9%. The rate of IVH grades II through IV and NEC with bowel perforation decreased with increasing gestational age, but the incidence of RDS did not differ significantly between GWs 24 to 29. A total of 5 infants (2%) needed a shunt operation because of posthemorrhagic ventricular dilatation. Two hundred eleven ELBW infants (40% of all and 60% of live-born infants) survived until discharge or to the age corresponding with 40 GWs. The oxygen dependency rate at the age corresponding to 36 GWs was 39%, and 9% had ROP stage III-V. Neurological status was considered completely normal in 74% of the surviving infants. The proportions of infants born at 22 to 23, 24 to 25, 26 to 27, and 28 to 29 GWs with at least one disability (ROP, oxygen dependency, or abnormal neurological status) at the age corresponding to 36 GWs were 100%, 62%, 51%, and 45%, respectively. Birth weight <600 g and gestational age <25 GWs were the independent risks for death and short-term disability. The primary risk factor for IVH grades II through IV was RDS. Low 5-minute Apgar scores predicted poor prognosis, ie, death or IVH, and antenatal steroid treatment to mothers with threatening premature labor seemed to protect infants against these. Some differences were found in the mortality rates between the 5 university hospital districts: neonatal mortality was significantly lower (25% vs 44%) in one university hospital area and notably higher (53% vs 34%) in another area. Furthermore, significant differences were also found in morbidity, ie, oxygen dependency and ROP rates. Differences in perinatal (79% vs 45%) and neonatal (59% vs 32%) mortality rates were found between secondary and tertiary level hospitals. CONCLUSION: Our study shows that even with modern perinatal technology and care, intrauterine and early deaths of ELBW infants are common. The outcome of infants born at 22 to 23 GWs was unfavorable, but the prognosis improved rapidly with increasing maturity. The clear regional and hospital level differences detected in survival rates and in short-term outcome of ELBW infants emphasizes that the mortality and morbidity rates should be continuously followed and that differences should be evaluated in perinatal audit procedures. (ABSTRACT TRUNCATED)

The role of cerebral microdialysis in predicting the outcome after experimental hypothermic circulatory arrest.

OBJECTIVE: To evaluate whether and which of the cerebral microdialysis parameters are predictive of postoperative outcome after an experimental 75-min period of hypothermic circulatory arrest (HCA) in a chronic porcine model. DESIGN: Seventy-four juvenile female pigs underwent a 75-min period of HCA at 20 degrees C. A microdialysis catheter was placed into the cortex gray matter and brain extracellular concentrations of glucose, lactate, glycerol and glutamate were measured throughout the experiment by enzymatic methods using a microdialysis analyzer. Surviving animals were sacrificed on the 7th postoperative day and histopathological examination of the brain was performed. RESULTS: Brain glucose concentrations were higher in animals that survived (p = 0.017), especially from the 90-min until the 7-h interval after the start of rewarming. The blood venous concentrations of glucose were also higher among survivors, and correlated significantly with the brain glucose levels at 2-h and 4-h intervals after the start of rewarming. Higher concentrations of brain lactate, glycerol and glutamate were observed throughout the study among animals that died postoperatively. Brain glutamate and glycerol concentrations were significantly, negatively correlated with brain glucose concentrations. The lactate/glucose ratio was significantly lower among survivors during the postoperative period (p=0.014). Furthermore, brain glucose concentrations were higher and brain glycerol concentrations lower among the animals that did not develop brain infarction, but such differences did not reach statistical significance. CONCLUSION: Cerebral microdialysis is a useful tool for cerebral monitoring during experimental HCA. Low brain glucose concentrations and high brain lactate/glucose ratios after HCA are strong predictors of postoperative death. Brain glucose concentrations are negatively correlated with brain glycerol and glutamate concentrations.

Leukocyte filtration improves brain protection after a prolonged period of hypothermic circulatory arrest: A study in a chronic porcine model.

BACKGROUND: Ischemic cerebral injury follows a well-attested sequence of events, including 3 phases: depolarization, biochemical cascade, and reperfusion injury. Leukocyte infiltration and cytokine-mediated inflammatory reaction are known to play a pivotal role in the reperfusion phase. These events exacerbate the brain injury by impairing the normal microvascular perfusion and through the release of cytotoxic enzymes. The aim of the present study was to determine whether a leukocyte-depleting filter (LeukoGuard LG6, Pall Biomedical, Portsmouth, United Kingdom) could improve the cerebral outcome after hypothermic circulatory arrest. METHODS: Twenty pigs (23-30 kg) were randomly assigned to undergo cardiopulmonary bypass with or without a leukocyte-depleting filter before and after a 75-minute period of hypothermic circulatory arrest at 20 degrees C. Electroencephalographic recovery, S-100beta protein levels, and cytokine levels (interleukin 1beta, interleukin 8, and tumor necrosis factor alpha) were recorded up to the first postoperative day. Postoperatively, all animals were evaluated daily until death or until electively being put to death on day 7 by using a quantitative behavioral score. A postmortem histologic analysis of the brain was carried out on all animals. RESULTS: The rate of mortality was 2 of 10 in the leukocyte-depletion group and 5 of 10 in control animals. The risk for early death in control animals was 2.5 (95% confidence interval, 0.63-10.0) times higher than that of the leukocyte-depleted animals. The median behavioral score at day 7 was higher in the leukocyte-depletion group (8.5 vs 3.5; P =.04). The median of total histopathologic score was 8.5 in the leukocyte-depletion group and 15.5 in the control group (P =.005). CONCLUSION: A leukocyte-depleting filter improves brain protection after a prolonged period of hypothermic circulatory arrest.

Lamotrigine improves cerebral outcome after hypothermic circulatory arrest: a study in a chronic porcine model.

BACKGROUND: Glutamate excitotoxicity has an important role in the development of brain injury after prolonged hypothermic circulatory arrest. The goal of the present studies was to determine the potential efficacy of lamotrigine, an Na(+) channel blocker, to mitigate cerebral injury after hypothermic circulatory arrest. METHODS: Sixteen pigs (21-27 kg) were randomly assigned to receive lamotrigine (20 mg/kg) or placebo in a blinded fashion before a 75-minute period of hypothermic circulatory arrest (20 degrees C). Hemodynamic, electroencephalographic, and metabolic monitoring were carried out. S-100beta protein was determined up to the first postoperative morning. Daily behavioral assessment was performed until the animal died or was put to death on day 7. Histologic analysis of the brain was carried out in all animals. RESULTS: Complete behavioral recovery was seen in 5 of 8 (63%) animals after lamotrigine administration, compared with 1 of 8 (13%) in the placebo group (P =.02). Among the animals that survived for 7 days, the median behavioral score was higher in the lamotrigine group (8 vs 7, P =.02). The medians of recovered electroencephalographic bursts in the lamotrigine group were higher than those in the placebo group 4 1/2 hours after the start of rewarming (P =.01). The median S-100beta level was lower in the lamotrigine group (0.01 microg/L) than in placebo controls (0.1 microg/L) 20 hours after the start of rewarming (P =.01). The median of total histopathologic score was 5.5 in the lamotrigine group and 7.5 in the placebo group (P =.06). CONCLUSIONS: The present data suggest that lamotrigine improves neurologic outcome after a prolonged period of hypothermic circulatory arrest.

Randomized trial comparing natural and synthetic surfactant: increased infection rate after natural surfactant?

The efficacy of a natural porcine surfactant and a synthetic surfactant were compared in a randomized trial. In three neonatal intensive care units, 228 neonates with respiratory distress and a ratio of arterial to alveolar partial pressure of oxygen <0.22 were randomly assigned to receive either Curosurf 100 mgkg-1 or Exosurf Neonatal 5 ml.kg-1. After Curosurf, the fraction of inspired oxygen was lower from 15 min (0.45 +/- 0.22 vs 0.70 +/- 0.22, p = 0.0001) to 6 h (0.48 +/- 0.26 vs 0.64 +/- 0.23, p = 0.0001) and the mean airway pressure was lower at 1 h (8.3 +/- 3.2 mm H20 vs 9.4 +/- 3.1 mm H20, p = 0.01). Thereafter the respiratory parameters were similar. The duration of mechanical ventilation (median 6 vs 5 d) and the duration of oxygen supplementation (median 5 vs 4 d) were similar for Curosurf and Exosurf. After Curosurf, C-reactive protein value over 40 mg l-1 occurred in 45% (vs 12%; RR 3.62, 95%CI 2.12-6.17, p = 0.001), leukopenia in 52% (vs 28%; RR 1.85, 95% CI 1.31-2.61, p = 0.001) and bacteraemia in 11% (vs 4%; RR 3.17, 95% CI 1.05-9.52, p < 0.05). We conclude that when given as rescue therapy Curosurf had no advantage compared with Exosurf in addition to the more effective initial response. Curosurf may increase the risk of infection.

Intermittent retrograde cerebral perfusion during prolonged period of hypothermic circulatory arrest: a study in a chronic porcine model.

Previous studies have shown that although retrograde cerebral perfusion (RCP) improves cerebral outcome during hypothermic circulatory arrest (HCA), RCP exposes the brain to subsequent edema. In this study, we have compared intermittent RCP (I-RCP) with continuous RCP (C-RCP) and HCA alone to determine whether the rate of fluid sequestration can be decreased without losing the beneficial effects of RCP. Eighteen pigs were randomly assigned to undergo 75 min of I-RCP, C-RCP or HCA at 20 degrees C. Hemodynamic and metabolic measurements were carried out for upto 20 h. Behavioral assessments were examined until day 7, when histopathologic analysis of the brain was performed. The median amount of fluid sequestered was 145 ml after C-RCP and -50 ml after I-RCP (p = 0.04). The mean brain weight of the animals that died within the first postoperative day was significantly higher than that in electively sacrificed animals in the C-RCP group (p = 0.04). These data suggest that if RCP is implemented intermittently, the rate of cerebral edema can be decreased, without compromising the benefits of this strategy.

Diminished inducible nitric oxide synthase expression in fulminant early-onset neonatal pneumonia.

OBJECTIVE: Fulminant early-onset neonatal pneumonia is associated with ascending intrauterine infection (IUI), prematurity, persistent pulmonary hypertension (PPHN), and septicemia. Nitric oxide (NO) as an inflammatory mediator is included in antimicrobial defense and has a role in pathogenesis of septic shock. The aim was to study the role of inflammatory NO in neonatal pneumonia. METHODS: Lungs from 36 autopsies were studied: 12 had fulminant early-onset neonatal pneumonia, 5 pneumonia of later onset, and 19 controls had similar gestational and postnatal age. In addition, airway specimens from 21 intubated newborns were analyzed: 7 with fulminant early-onset pneumonia, 7 apparently noninfected infants born prematurely attributable to IUI, and 7 premature infants of similar gestation. Specimens were analyzed for inducible NO synthase (NOS2) and nitrotyrosine, an indicator of NO toxicity. The degree of staining was analyzed. RESULTS: In fulminant pneumonia, alveolar macrophages (AM) showed significantly less NOS2 immunoactivity than the controls. In the airway specimens, the infants with fulminant pneumonia 0 to 2 days after birth had significantly lower intracellular NOS2 and nitrotyrosine and significantly lower interleukin-1beta and surfactant protein-A than apparently noninfected IUI infants. NOS2 and the other indices increased significantly during the recovery. CONCLUSIONS: For the first time, we report NOS2 expression by macrophages from human neonates. In fulminant early-onset neonatal pneumonia, delayed production rather than excess of pulmonary inflammatory NO is associated with severe symptoms.

Is maintained cranial hypothermia the only factor leading to improved outcome after retrograde cerebral perfusion? An experimental study with a chronic porcine model.

BACKGROUND: Previous studies have shown that retrograde cerebral perfusion can improve neurologic outcome after prolonged hypothermic circulatory arrest. Here we have compared two temperatures of retrograde cerebral perfusion (15 degrees C and 25 degrees C) with hypothermic circulatory arrest at systemic hypothermia of 25 degrees C to clarify whether the possible benefit of retrograde cerebral perfusion may only be due to improved cooling effect. METHODS: Eighteen pigs (23-27 kg) were randomly assigned to undergo 15 degrees C retrograde cerebral perfusion at systemic hypothermia of 25 degrees C, 25 degrees C retrograde cerebral perfusion at 25 degrees C systemic hypothermia, or hypothermic circulatory arrest at 25 degrees C for 40 minutes. Flow was adjusted to maintain superior vena cava pressure at 20 mm Hg during retrograde cerebral perfusion. Hemodynamic, electrophysiologic, metabolic, and temperature monitoring were performed until 4 hours after the start of rewarming. Daily behavioral assessment was done until death or until the animals were killed on day 7. Histopathologic analysis of the brain was carried out on all animals. RESULTS: Epidural temperatures were lower in the 15 degrees C retrograde cerebral perfusion group during the intervention (P <.05). In the 15 degrees C retrograde cerebral perfusion group, 4 (67%) of 6 animals survived for 7 days compared with 3 (50%) of 6 in both the 25 degrees C retrograde cerebral perfusion and hypothermic circulatory arrest groups. The median total histopathologic score was 5 in the 15 degrees C retrograde cerebral perfusion group and 7 in the 25 degrees C retrograde cerebral perfusion group (P =.04). CONCLUSIONS: These findings suggest that enhanced cranial hypothermia is the major beneficial factor of retrograde cerebral perfusion when careful attention is paid to its implementation.

Serum S-100beta protein predicts brain injury after hypothermic circulatory arrest in pigs.

OBJECTIVE: Serum S-100beta protein is suggested to be a neurobiochemical marker of brain injury after cardiac and aortic arch surgery. The aim of the present study was to investigate the predictive value of S-100beta protein with respect to histopathological analysis of the brain after a prolonged period of hypothermic circulatory arrest (HCA). METHODS: Eighteen pigs (21 to 31 kg) underwent a 75 min period of HCA at 20 degrees C. Serum concentrations of S-100beta were assayed in mixed venous blood before and 2, 4, 7 and 20 h after HCA. A semiquantitative post-mortem histopathological analysis scoring all main regions of the brain was carried out in every animal. RESULTS: All animals were stable during and after cardiopulmonary bypass (CPB) and survived at least to the first postoperative day. Ten of the 18 animals survived 7 days after surgery and were electively sacrificed. Animals with severe histopathological injury showed higher serum S-100beta protein levels at every time point after HCA. The strongest correlation between the total histopathologic score and serum S-100beta levels was found at 7 h after HCA (tau = 0.422 and p = 0.023). CONCLUSION: Serum S-100beta protein levels correlate with histopathological injury after a prolonged period of HCA in pigs. This finding supports the results of previous studies suggesting the potential accuracy of S-100beta in the prediction of brain injury after cardiac surgery.

Cold retrograde cerebral perfusion improves cerebral protection during moderate hypothermic circulatory arrest: A long-term study in a porcine model.

BACKGROUND: Deep hypothermic circulatory arrest is an effective method of cerebral protection, but it is associated with long cardiopulmonary bypass times and coagulation disturbances. Previous studies have shown that retrograde cerebral perfusion can improve neurologic outcomes after prolonged hypothermic circulatory arrest. We tested the hypothesis that deep hypothermic retrograde cerebral perfusion could improve cerebral outcome during moderate hypothermic circulatory arrest. METHODS: Twelve pigs (23-29 kg) were randomly assigned to undergo either retrograde cerebral perfusion (15 degrees C) at 25 degrees C or hypothermic circulatory arrest with the head packed in ice at 25 degrees C for 45 minutes. Flow was adjusted to maintain superior vena cava pressure at 20 mm Hg throughout retrograde cerebral perfusion. Hemodynamic, electrophysiologic, metabolic, and temperature monitoring were carried out until 4 hours after the start of rewarming. Daily behavioral assessment was performed until elective death on day 7. A postmortem histologic analysis of the brain was carried out on all animals. RESULTS: In the retrograde cerebral perfusion group, 5 (83%) of 6 animals survived 7 days compared with 2 (33%) of 6 in the hypothermic circulatory arrest group. Complete behavioral recovery was seen in 4 (67%) animals after retrograde cerebral perfusion but only in 1 (17%) animal after hypothermic circulatory arrest. Postoperative levels of serum lactate were higher, and blood pH was lower in the hypothermic circulatory arrest group. There were no significant hemodynamic differences between the study groups. CONCLUSIONS: Cold hypothermic retrograde cerebral perfusion during moderate hypothermic circulatory arrest seems to improve neurologic outcome compared with moderate hypothermic circulatory arrest with the head packed in ice.

Short versus prolonged indomethacin therapy for patent ductus arteriosus in preterm infants.

OBJECTIVE: To evaluate whether a prolonged low-dose course of indomethacin would produce an improved closure rate and have fewer side effects compared with a short standard dosage schedule in the management of patent ductus arteriosus (PDA) in preterm infants. STUDY DESIGN: Sixty-one infants of gestational ages 24 to 32 weeks with a PDA confirmed with echocardiography were randomized to receive 0.2 to 0.1 to 0.1 mg/kg indomethacin in 24 hours (short course, n = 31) or 0.1 mg/kg every 24 hours 7 times (long course, n = 30). Echocardiography was done 3, 9, and 14 days after the treatment was started, and side effects were monitored. RESULTS: Primary PDA closure occurred more often in the short course group (94% vs 67%, P =.011), but the sustained closure rates were not different (74% vs 60%). Surgical PDA ligations were less frequent in the short course group than in the long course group. The short course group had a shorter duration of oxygen supplementation, less frequent symptoms of necrotizing enterocolitis, and a lower rate of urea retention. Mortality and other neonatal morbidity rates were similar. CONCLUSION: A prolonged low-dosage indomethacin regimen offers no advantage compared with a standard-dosage short course in the management of a hemodynamically significant PDA in preterm infants.

Overdoses of pethidine given to two preterm neonates.

This paper reports two mechanically ventilated preterm babies who received overdoses of pethidine in the neonatal period. One of the neonates (gestational age 26 weeks, birthweight 1040 g) received repeated appropriate doses, which resulted in central nervous system irritability and convulsion due to accumulation of the drug and its metabolite, norpethidine. The other neonate (gestational age 27 weeks, birthweight 980 g) received a major (10-fold) overdose with little clinical effect. These two cases indicate notable individual variability in the responses of babies to pethidine. This is typical of other opioids, too. Therefore, the dosing of opioids to neonates should be titrated individually, and the patients should be observed carefully.