pancuronium and Cerebral-Hemorrhage

Ventilated newborn infants breathing in asynchrony with the ventilator are at risk for complications during mechanical ventilation, such as pneumothorax or intraventricular hemorrhage, and are exposed to more severe barotrauma, which consequently could impair their clinical outcome. Neuromuscular paralysis, which eliminates spontaneous breathing efforts of the infant, has potential advantages in this respect. However, a number of complications have been reported with muscle relaxation in infants, so that concerns exist regarding the safety of prolonged neuromuscular paralysis in newborn infants.. To determine whether routine neuromuscular paralysis of newborn infants receiving mechanical ventilation compared with no routine paralysis results in clinically important benefits or harms.. The Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1, 2004), MEDLINE (from 1966 to April 2004) and EMBASE (from 1988 to April 2004) were searched. References of review articles were hand searched. Language restriction was not imposed.. All trials using random or quasi-random patient allocation, in which the routine use of neuromuscular blocking agents during mechanical ventilation was compared to no paralysis or selective paralysis in newborn infants. Methodological quality was assessed blindly and independently by the two authors.. Data were abstracted using standard methods of the Cochrane Collaboration and its Neonatal Review Group, with independent evaluation of trial quality, and abstraction and synthesis of data by both authors. Treatment effect was analysed using relative risk, risk difference and weighted mean difference.. Ten possibly eligible trials were identified, of which six were included in the review. All the included trials studied preterm infants ventilated for respiratory distress syndrome, and used pancuronium as the neuromuscular blocking agent. In the analysis of the results of all trials, no significant difference was found in mortality, air leak or chronic lung disease, but there was a significant reduction in intraventricular hemorrhage and a trend towards less severe intraventricular hemorrhages. In the subgroup analysis of trials studying a selected population of ventilated infants with evidence of asynchronous respiratory efforts, a significant reduction in intraventricular hemorrhage (any grade and severe IVH) was found, and a trend towards less air leak. In the subgroup analysis of trials studying an unselected population of ventilated infants, no significant differences were found for any of the outcomes.. For ventilated preterm infants with evidence of asynchronous respiratory efforts, neuromuscular paralysis with pancuronium seems to have a favourable effect on intraventricular hemorrhage and possibly on air leak. Uncertainty remains, however, regarding the long term pulmonary and neurologic effects, and regarding the safety of prolonged use of pancuronium in ventilated newborn infants. There is no evidence from randomized trials on the effects of neuromuscular blocking agents other than pancuronium. The routine use of pancuronium or any other neuromuscular blocking agent in ventilated newborn infants cannot be recommended based on current evidence.

Topics: Cerebral Hemorrhage; Humans; Infant, Newborn; Infant, Premature; Neuromuscular Blockade; Neuromuscular Nondepolarizing Agents; Outcome Assessment, Health Care; Pancuronium; Pneumothorax; Randomized Controlled Trials as Topic; Respiration, Artificial; Respiratory Distress Syndrome, Newborn

Ventilated newborn infants breathing in asynchrony with the ventilator are at risk for complications during mechanical ventilation, such as pneumothorax or intraventricular hemorrhage, and are exposed to more severe barotrauma, which consequently could impair their clinical outcome. Neuromuscular paralysis, which eliminates spontaneous breathing efforts of the infant, has potential advantages in this respect. However, a number of complications have been reported with muscle relaxation in infants, so that concerns exist regarding the safety of prolonged neuromuscular paralysis in newborn infants.. To determine whether routine neuromuscular paralysis of newborn infants receiving mechanical ventilation compared with no routine paralysis results in clinically important benefits or harms.. MEDLINE (from 1966 to May 2000) and EMBASE (from 1988 to May 2000) were searched, as well as The Cochrane Controlled Trials Register (issue 2, 2000). References of review articles were hand searched. Language restriction was not imposed.. All trials using random or quasi-random patient allocation, in which the routine use of neuromuscular blocking agents during mechanical ventilation was compared to no paralysis or selective paralysis in newborn infants. Methodological quality was assessed blindly and independently by the two authors.. Data were abstracted using standard methods of the Cochrane Collaboration and its Neonatal Review Group, with independent evaluation of trial quality, and abstraction and synthesis of data by both authors. Treatment effect was analysed using relative risk, risk difference and weighted mean difference.. Ten possibly eligible trials were identified, of which five were included in the review. All the included trials studied preterm infants ventilated for respiratory distress syndrome, and used pancuronium as the neuromuscular blocking agent. In the analysis of the results of all trials, no difference was found in mortality, air leak or chronic lung disease, but there was a significant reduction in intraventricular hemorrhage and a trend towards less severe intraventricular hemorrhages. In the subgroup analysis of trials studying a selected population of ventilated infants with evidence of asynchronous respiratory efforts, a significant reduction in intraventricular hemorrhage (any grade and severe IVH) was found, and a trend towards less air leak. In the subgroup analysis of trials studying an unselected population of ventilated infants, no differences were found for any of the outcomes.. For ventilated preterm infants with evidence of asynchronous respiratory efforts, neuromuscular paralysis with pancuronium seems to have a favourable effect on intraventricular hemorrhage and possibly on air leak. Uncertainty remains, however, regarding the long term pulmonary and neurologic effects, and regarding the safety of prolonged use of pancuronium in ventilated newborn infants. There is no evidence from randomized trials on the effects of neuromuscular blocking agents other than pancuronium. Therefore, the routine use of pancuronium or any other neuromuscular blocking agent in ventilated newborn infants cannot be recommended based on current evidence.

Topics: Cerebral Hemorrhage; Humans; Infant, Newborn; Infant, Premature; Neuromuscular Blockade; Neuromuscular Nondepolarizing Agents; Outcome Assessment, Health Care; Pancuronium; Pneumothorax; Randomized Controlled Trials as Topic; Respiration, Artificial; Respiratory Distress Syndrome, Newborn

Recent progress in understanding the pathophysiology of hypoxic-ischemic encephalopathies and intraventricular hemorrhages have enabled us to propose new therapeutic modalities in preventing the development and severity of these disorders in the newborn. Because neuronal damage may be reversible under certain conditions, appropriate evaluation of these drugs (single or in combination) is very important in the continuous attempt to ameliorate the neurodevelopmental outcome of these infants. An interventionist attitude should prove to be a better alternative than a supportive one.

Topics: Asphyxia Neonatorum; Barbiturates; Brain Ischemia; Cerebral Hemorrhage; Female; Fetal Hypoxia; Humans; Indomethacin; Infant; Infant, Newborn; Pancuronium; Pregnancy

Topics: Cerebral Hemorrhage; Cerebrovascular Circulation; Clinical Trials as Topic; Ethamsylate; Humans; Indomethacin; Infant, Newborn; Infant, Premature, Diseases; Pancuronium; Phenobarbital; Risk; Vitamin E

Fifty-one sequential intubated babies with birth weights of less than 1,751 were evaluated by serial Doppler ultrasound during the first three days of life. These babies were part of a phenobarbital prophylaxis trial cohort study. Subependymal-intraventricular hemorrhage developed in 17 of the babies. Infants with subependymal-intraventricular hemorrhage, whether or not they received pancuronium or phenobarbital, had coefficients of variation comparable to those of babies without hemorrhage. Coefficient of variation values of the right were comparable to values obtained from the left anterior cerebral artery complex and did not appear to be consistently altered by the presence of subependymal-intraventricular hemorrhage. Coefficient of variation values appeared to be consistently greatest on day 1 and lowest on day 2. In addition, the values overall increased as the number of waves used to determine the coefficient of variation enlarged from five to 20. This phenomena, however, was not seen among pancuronium recipients and suggests that movement artifact may be a determinant of coefficient of variation values. We conclude that, when the best 20 waves are chosen to evaluate the coefficient of variation, no association exists between coefficient of variation values and development of subependymal-intraventricular hemorrhage or administration of phenobarbital.

Topics: Blood Flow Velocity; Cerebral Hemorrhage; Cerebrovascular Circulation; Clinical Trials as Topic; Cohort Studies; Humans; Infant, Newborn; Pancuronium; Phenobarbital

Topics: Cerebral Hemorrhage; Cerebrovascular Circulation; Clinical Trials as Topic; Ethamsylate; Humans; Indomethacin; Infant, Newborn; Infant, Premature, Diseases; Pancuronium; Phenobarbital; Risk; Vitamin E

In a previous study of preterm infants requiring mechanical ventilation for the respiratory distress syndrome, we demonstrated a striking association of fluctuating cerebral blood-flow velocity in the first day of life with the subsequent occurrence of intraventricular hemorrhage. Because this fluctuating pattern could be eliminated by muscle paralysis, we conducted a prospective study of preterm infants receiving mechanical ventilation for the respiratory distress syndrome in which we evaluated the effect of paralysis and this flow-velocity pattern on the incidence and severity of intraventricular hemorrhage. Twenty-four infants with the fluctuating pattern in the first hours of life were identified and randomly selected to serve as controls (10) or to be subjected to muscle paralysis (14). Intraventricular hemorrhage developed in all 10 control infants but in only 5 of the 14 infants subjected to muscle paralysis. Moreover, in 4 of the 5 paralyzed infants in whom hemorrhage developed, it did so after cessation of the paralysis. Seven of the 10 control infants had Grade III hemorrhage, the most severe variety of intraventricular hemorrhage, whereas none of the paralyzed infants had Grade III hemorrhage. We conclude that elimination of fluctuating cerebral blood-flow velocity in preterm infants with respiratory distress syndrome markedly reduces the incidence and severity of intraventricular hemorrhage.

Topics: Blood Flow Velocity; Cerebral Hemorrhage; Cerebrovascular Circulation; Clinical Trials as Topic; Humans; Infant, Newborn; Muscles; Pancuronium; Prospective Studies; Respiration, Artificial; Respiratory Distress Syndrome, Newborn; Ultrasonography

Topics: Cerebral Hemorrhage; Clinical Trials as Topic; Humans; Infant, Newborn; Infant, Premature, Diseases; Pancuronium; Respiration, Artificial; Respiratory Distress Syndrome, Newborn

Topics: Blood Flow Velocity; Blood Pressure; Cerebral Hemorrhage; Cerebrovascular Circulation; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Pancuronium

Doppler flow velocity (DFV) in the anterior cerebral artery was recorded every 12 h and cerebral perfusion pressure (CPP) continuously in 21 sick, ventilated preterm neonates for 48 h from shortly after birth. Ten received a neuromuscular blocker, seven were sedated with morphine infusions and five received neither of these treatments. Variability of DFV and CPP was assessed by the coefficient of variation (CV) and the autocorrelation function (ACF). Variability of both signals was lowest in the group treated by neuromuscular blockade (DFV CV 3, s.d. = 0.8; CPP CV 9, s.d. = 2.2; CPP ACF 37, s.d. = 19.2), intermediate in the group receiving sedation by morphine infusion (DFV CV 3.4, s.d. = 0.7; CPP CV 11, s.d. = 2.2; CPP ACF 31, s.d. = 21.6) and highest in the group receiving neither treatment (DFV CV 5, s.d. = 1.8; CPP CV 14, s.d. = 2.3; CPP ACF 27, s.d. = 16.7). Variability also increased with decreasing gestational age, suggesting that immature cerebrovascular regulatory mechanisms were present in the least mature neonates.

Topics: Birth Weight; Cerebral Arteries; Cerebral Hemorrhage; Cerebrovascular Circulation; Gestational Age; Humans; Infant, Low Birth Weight; Infant, Newborn; Infant, Premature; Morphine; Pancuronium; Ultrasonography

A total of 22 infants of less than 31 weeks' gestation who were mechanically ventilated for a minimum of 12 hours for respiratory distress syndrome were studied. The coefficient of variation of direct systolic pressure was measured each minute from six to 36 hours of age and averaged per hour after birth with a microcomputer-based system of data collection. At the start of recording, the ultrasound scan appeared normal in each infant, but intraventricular hemorrhage developed in ten infants less than 36 hours of age. Twelve infants remained free of intraventricular hemorrhages. BP fluctuation was greater for a longer proportion of measured time in infants in whom intraventricular hemorrhage did not develop compared with those in whom it did develop P less than .05). These findings do not support a causal relationship between BP fluctuation and intraventricular hemorrhage within the range of coefficient of variation studied.

Topics: Blood Pressure; Cerebral Hemorrhage; Female; Gestational Age; Humans; Infant, Newborn; Infant, Premature; Male; Pancuronium; Respiration, Artificial; Respiratory Distress Syndrome, Newborn

The venous circulatory changes in 12 intubated premature infants with fluctuations or elevations in arterial BP were studied. The objectives of the study were to determine whether important alterations in venous pressure occur in infants with fluctuations in arterial BP or with elevations in arterial BP associated with suctioning. Venous and arterial catheters were present in all infants. Perfusion pressure was derived from the difference between mean arterial BP and venous pressure. At rest, minimal change in arterial BP, venous pressure, and perfusion pressure was observed. Elevations in arterial BP were accompanied by pronounced changes in venous pressure. However, because the magnitude and the direction of the changes in venous pressure were not consistent, pronounced changes in perfusion pressure resulted. Fluctuations in arterial BP were associated with fluctuations in venous pressure, which also resulted in pronounced and continuous alterations in perfusion pressure. Induced muscle paralysis in two infants obliterated the changes in arterial BP, venous pressure, and perfusion pressure associated with suctioning. These data demonstrate that marked venous circulatory changes accompany common arterial circulatory abnormalities; such alterations on the venous side of the circulation may be important in the pathogenesis of neonatal hemorrhagic and/or ischemic injury.

Topics: Blood Pressure; Brain Ischemia; Cerebral Hemorrhage; Humans; Infant, Newborn; Infant, Premature; Pancuronium; Paralysis; Prospective Studies; Respiration, Artificial; Respiratory Distress Syndrome, Newborn; Rest; Sucking Behavior; Venous Pressure

Topics: Blood Flow Velocity; Cerebral Hemorrhage; Cerebral Ventricles; Cerebrovascular Circulation; Humans; Infant, Newborn; Infant, Premature, Diseases; Pancuronium; Respiratory Distress Syndrome, Newborn

Topics: Cerebral Hemorrhage; Humans; Infant, Newborn; Infant, Premature, Diseases; Pancuronium; Pneumothorax