Use of Nitric Oxide in newborn with pulmonary hypertension
Pulmonary hypertension of the new born (PPHN) is one of the complications that threaten the life of the new born. In fetal life, there is a very low flow of pulmonary blood resulting to not more than 10% of the fetal cardiac output going to the lungs of the fetus. This is due to the high pulmonary vascular resistance when compared with systemic vascular resistance of the fetus. This is considered as a serious disorder which constricts the arteries of the new born after delivery and therefore it limits the flow of blood to the lungs which in turn affect the amount of oxygen which is reaching the blood stream. Like any other condition affecting the breathing system, this is a serious disorder which threatens the life of the infant. In the fetal stage, the placenta plays a crucial role in eliminating carbon dioxide and transportation of oxygen in the blood stream and therefore the lungs are not in dire need of increased blood flow. When the umbilical cord ceases to play this major role after birth, the lungs must adapt to the new role and their air sacs will have to be filled with air while blood arteries to the lungs need to widen to supply adequate amount of blood.
This condition results to systemic arterial hypoxemia due to increased pulmonary vascular resistance and the mechanism of right to left shunting of the deoxygenated blood. The use of inhaled nitric oxide in decreasing the level of pulmonary vascular resistance has been a long term debate owing to the expected balance between the risk involved and the expected results. In this paper we are going to review research one whether inhaled nitric oxide really decrease hypoxemia in infants who develop PPH and the associated risk to come up with a conclusion whether it is really a health risk to use nitric oxide in these infants.
The subject of transition of life from the womb to the outside world has been a subject of interest in the field of medicine especially to Neonatologists. PPHN is one of the most complications that they face when dealing with newborns, which has been the main reason for heightened research about the subject. There are a number of researches which has linked the development of the PPHN condition with the ability of the infant to generate nitric oxide compound.
What is the relationship between nitric oxide and PPHN. Nitric oxide is compounds that can reduce blood pressure and has long been used to treat infant with PPHN. The compound, nitric oxide, is produced in the body through synthesis from arginine which is one of the essential body amino acid. The action of argnines needs Citrulline as a precursor. Therefore inadequate supply of arginine and citrulline would automatically result to reduced supply of nitric oxide which increasingly predisposes the infant to condition like PPHN. The infant fails to meet the threshold level of nitric oxide which is required for a successive transition of a functioning lung.
However the use of nitric oxide in correcting PPHN condition has remained a controversial subject, with some studies documenting the effectiveness of the therapy while others documenting reduced effectiveness in light of the risk and cost of the therapy. However, nitric oxide remains the most preferred way to deal with the condition.
Does the use of inhaled nitric oxide improve oxygenation? Let us look at one of the study that was published in The New England Journal of Medicine. In this study, Jesse et al., (1997) carried out study looking into whether inhaled nitric oxide was effective in decreasing hypoxemia in infants who had PPHN condition.
This was a prospective multimember study in which 58 full term infants who had all developed PPHN condition were recruited. They were in turn randomly assigned controlled nitrogen gas or nitric oxide at a concentration of 80 ppm with oxygen. They were to breath through a ventilator. In evaluation of the study, the treatment was evaluated as successful in case there increase in oxygenation after every 20 minutes coupled with constant measure of systemic blood pressure. In this case it was continued at a lower concentration. If it was found out that there was no remarkable increase in oxygenation, the trials were discontinued and an alternative therapy employed through extracorporeal membrane oxygenation.
From the study, the results revealed that the use of inhaled nitric oxide resulted in doubling of systemic oxygenation in 53% of the patient (16 out of the 30 infants). It also documented that the use of conventional therapy which was done without nitric oxide lead to an increased oxygenation by 7% (2 out of 18 infants).
After the continuation of the study in successful trial, the long term use of nitric oxide therapy had a sustained systemic oxygenation in 75% of the infants who recorded improvement in the beginning. On the other hand 71 % of the infants in the control group and 40% of the infant in the nitric oxide group required therapy with extracorporeal member oxygenation. The study also showed that the number of death resulting from the two therapy were equal. Contrary to the expected harms of the therapy, inhaled nitric oxide did not result in systemic hypotension or increased levels of methemoglobin.
The study concluded that inhaled nitric oxides leads to improved systemic oxygenation and therefore it can be used as an effective therapy for infants with persistent pulmonary hypertension. This study also concluded that nitric oxide therapy can be used to reduce the use of other invasive treatment which poses more threats to the chance of survival of the infant.
This study replicated the results which have been found in other studies previously. Kinsella (1997) had also found the underlying mechanism that could be used to explain the action of nitric acid. He showed that nitric oxide activated guanylate oxide which in turn results to increase Cyclic-GMP levels in the smooth muscle. This prohibits myosin protein from cross-bridging formation n the smooth muscles resulting to vascular relaxation.
Compared to other therapies which have bee proposed, the use of nitric oxide has been highly recommended. Tolsa (1995) argued that despite proposing the use of magnesium sulphate, its effectiveness could not be compared to the use of nitric oxide. The same findings were also highlighted by Wu (1995) in the study of the use of magnesium sulphate and by Vosatka (1994) in the study on the use of arginine fusion.
This condition results to systemic arterial hypoxemia due to increased pulmonary vascular resistance and the mechanism of right to left shunting of the deoxygenated blood. The use of inhaled nitric oxide in decreasing the level of pulmonary vascular resistance has been a long term debate owing to the expected balance between the risk involved and the expected results. In this paper we are going to review research one whether inhaled nitric oxide really decrease hypoxemia in infants who develop PPH and the associated risk to come up with a conclusion whether it is really a health risk to use nitric oxide in these infants.
Nitric oxide can help infants with PPHN
The subject of transition of life from the womb to the outside world has been a subject of interest in the field of medicine especially to Neonatologists. PPHN is one of the most complications that they face when dealing with newborns, which has been the main reason for heightened research about the subject. There are a number of researches which has linked the development of the PPHN condition with the ability of the infant to generate nitric oxide compound.
What is the relationship between nitric oxide and PPHN. Nitric oxide is compounds that can reduce blood pressure and has long been used to treat infant with PPHN. The compound, nitric oxide, is produced in the body through synthesis from arginine which is one of the essential body amino acid. The action of argnines needs Citrulline as a precursor. Therefore inadequate supply of arginine and citrulline would automatically result to reduced supply of nitric oxide which increasingly predisposes the infant to condition like PPHN. The infant fails to meet the threshold level of nitric oxide which is required for a successive transition of a functioning lung.
However the use of nitric oxide in correcting PPHN condition has remained a controversial subject, with some studies documenting the effectiveness of the therapy while others documenting reduced effectiveness in light of the risk and cost of the therapy. However, nitric oxide remains the most preferred way to deal with the condition.
Does the use of inhaled nitric oxide improve oxygenation? Let us look at one of the study that was published in The New England Journal of Medicine. In this study, Jesse et al., (1997) carried out study looking into whether inhaled nitric oxide was effective in decreasing hypoxemia in infants who had PPHN condition.
This was a prospective multimember study in which 58 full term infants who had all developed PPHN condition were recruited. They were in turn randomly assigned controlled nitrogen gas or nitric oxide at a concentration of 80 ppm with oxygen. They were to breath through a ventilator. In evaluation of the study, the treatment was evaluated as successful in case there increase in oxygenation after every 20 minutes coupled with constant measure of systemic blood pressure. In this case it was continued at a lower concentration. If it was found out that there was no remarkable increase in oxygenation, the trials were discontinued and an alternative therapy employed through extracorporeal membrane oxygenation.
From the study, the results revealed that the use of inhaled nitric oxide resulted in doubling of systemic oxygenation in 53% of the patient (16 out of the 30 infants). It also documented that the use of conventional therapy which was done without nitric oxide lead to an increased oxygenation by 7% (2 out of 18 infants).
After the continuation of the study in successful trial, the long term use of nitric oxide therapy had a sustained systemic oxygenation in 75% of the infants who recorded improvement in the beginning. On the other hand 71 % of the infants in the control group and 40% of the infant in the nitric oxide group required therapy with extracorporeal member oxygenation. The study also showed that the number of death resulting from the two therapy were equal. Contrary to the expected harms of the therapy, inhaled nitric oxide did not result in systemic hypotension or increased levels of methemoglobin.
The study concluded that inhaled nitric oxides leads to improved systemic oxygenation and therefore it can be used as an effective therapy for infants with persistent pulmonary hypertension. This study also concluded that nitric oxide therapy can be used to reduce the use of other invasive treatment which poses more threats to the chance of survival of the infant.
This study replicated the results which have been found in other studies previously. Kinsella (1997) had also found the underlying mechanism that could be used to explain the action of nitric acid. He showed that nitric oxide activated guanylate oxide which in turn results to increase Cyclic-GMP levels in the smooth muscle. This prohibits myosin protein from cross-bridging formation n the smooth muscles resulting to vascular relaxation.
Compared to other therapies which have bee proposed, the use of nitric oxide has been highly recommended. Tolsa (1995) argued that despite proposing the use of magnesium sulphate, its effectiveness could not be compared to the use of nitric oxide. The same findings were also highlighted by Wu (1995) in the study of the use of magnesium sulphate and by Vosatka (1994) in the study on the use of arginine fusion.
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