Four patterns of response to inhaled nitric oxide for persistent pulmonary hypertension of the newborn.

OBJECTIVE: To determine the clinical role of inhaled nitric oxide (iNO) in the treatment of persistent pulmonary hypertension of the newborn (PPHN). STUDY DESIGN: Prospective open observational clinical study. SETTING: A regional cardiac and pediatric intensive care unit. METHODS: Twenty-five consecutive near-term neonates (> 35 weeks gestation) with severe PPHN (oxygenation index [OI] > 25) were given a trial of iNO of 20 ppm for 20 minutes. Neonates who showed a greater than 20% improvement in PaO2 as well as a decrease in the OI to below 40 were defined as responders and continued on this therapy. RESULTS: Four patterns of response emerged to the iNO therapy: Pattern 1 neonates (n = 2) did not respond to the initial trial of iNO-one survived. Pattern 2 neonates (n = 9) responded to the initial trial of iNO, but failed to sustain this response over 36 hours, as defined by a rise in the OI to > 40. Six survived, five with extracorporeal membrane oxygenation. Pattern 3 neonates (n = 11) responded to the initial trial of iNO, sustained this response, and were successfully weaned from iNO within 5 days--all survived to discharge. Pattern 4 neonates (n = 3) responded to the initial trial of iNO, but developed a sustained dependence on iNO for 3 to 6 weeks. All three died and lung histology revealed severe pulmonary hypoplasia and dysplasia. These neonates (pattern 4) not only required iNO for a longer period of time than did the sustained responders (pattern 3), but they required significantly higher doses of iNO during their first 5 days of iNO therapy. CONCLUSIONS: Early responses to iNO may not be sustained. Neonates with pulmonary hypoplasia and dysplasia may have a decreased sensitivity and differing time course of response to iNO when compared with patients who have PPHN in fully developed lungs.

Early response to inhaled nitric oxide and its relationship to outcome in children with severe hypoxemic respiratory failure.

OBJECTIVE: To examine whether the early response to inhaled nitric oxide (iNO) is a measure of reversibility of lung injury and patient outcome in children with acute hypoxemic respiratory failure (AHRF). DESIGN: Retrospective review study. SETTING: Pediatric ICUs. PATIENTS: Thirty infants and children, aged 1 month to 13 years (median, 7 months) with severe AHRF (mean alveolar arterial oxygen gradient of 568+/-9.3 mm Hg, PaO2/fraction of inspired oxygen of 56+/-2.3, oxygenation index [OI] of 41+/-3.8, and acute lung injury score of 2.8+/-0.1). Eighteen patients had ARDS. INTERVENTIONS: The magnitude of the early response to iNO was quantified as the percentage change in OI occurring within 60 min of initiating 20 ppm iNO therapy. This response was compared to patient outcome data. MEASUREMENTS AND RESULTS: There was a significant association between early response to iNO and patient outcome (Kendall tau B r=0.43, p < 0.02). All six patients who showed < 15% improvement in OI died; 4 of the 11 patients (36%) who had a 15 to 30% improvement in OI survived, while 8 of 13 (61%) who had a > 30% improvement in OI survived. Overall, 12 patients (40%) survived, 9 with ongoing conventional treatment including iNO, and 3 with extracorporeal support. CONCLUSIONS: In AHRF in children, greater early response to iNO appears to be associated with improved outcome. This may reflect reversibility of pulmonary pathophysiologic condition and serve as a bedside marker of disease stage.

Very-low-dose inhaled nitric oxide: a selective pulmonary vasodilator after operations for congenital heart disease.

Inhaled low-dose nitric oxide (2, 10, 20 ppm), together with high inspired oxygen concentration (0.80), was administered after corrective operations 13 times to 10 infants (median age 6 months) who were at risk of postoperative pulmonary hypertension because of their congenital heart disease and left-to-right shunt. Inhaled nitric oxide, even in a very low dose (2 ppm), caused selective pulmonary vasodilatation. The pulmonary/systemic artery pressure ratio was a predictor of the response to nitric oxide, with a greater response being seen in those with a high ratio (> or = 0.50). In children with a high pulmonary/systemic pressure ratio, the mean pulmonary vascular resistance index fell by 37% to 42%, accompanied by only a 10% fall in the systemic vascular resistance index but a 14% to 16% rise in mean cardiac index. No toxicity was seen in any subject. This exciting new therapy may prove to be an important adjunct in the management of postoperative pulmonary hypertension in the child with congenital heart disease.

Profound reduction in morphine clearance and liver blood flow in shock.

In six patients with septic shock apparent liver blood flow was significantly reduced compared with two patients restudied on recovery from shock and a group of four matched unshocked patients undergoing intensive care (287 +/- 23 ml/min vs 870 +/- 164 ml/min; mean +/- SEM). In the shocked patients the elimination half-life of morphine was significantly prolonged (13.2 +/- 3.5 h vs 5.9 +/- 1.4 h; mean +/- SEM) and the systemic clearance of morphine reduced by 53%, in comparison with the non-shocked patients. In both groups, morphine elimination was markedly delayed compared with previously reported observations in normal subjects and surgical patients. Care should be exercised with the use of drugs with a high hepatic extraction ratio in shocked patients.

Nitric oxide is superior to prostacyclin for pulmonary hypertension after cardiac operations.

BACKGROUND: Severe pulmonary hypertension is still a cause of morbidity and mortality in children after cardiac operations. The objective of this study was to compare the vasodilator properties of inhaled nitric oxide, a novel pulmonary vasodilator, and intravenous prostacyclin in the treatment of severe postoperative pulmonary hypertension. METHODS: Thirteen children (aged 3 days to 12 months) with severe pulmonary hypertension after cardiac operations were given inhaled nitric oxide (20 ppm x 10 minutes) and intravenous prostacyclin (20 ng.kg-1.min-1 x 10 minutes) in a prospective, randomized cross-over study. RESULTS: Both nitric oxide and prostacyclin resulted in a reduction in pulmonary arterial pressure, although the mean pulmonary arterial pressure was significantly lower during nitric oxide therapy (28.5 +/- 2.9 mm Hg) than during prostacyclin therapy (35.4 +/- 2.1 mm Hg; p < 0.05). The mean pulmonary to systemic arterial pressure ratio was also significantly lower during nitric oxide than prostacylin administration (0.46 +/- 0.04 versus 0.68 +/- 0.05; p < 0.01), due mainly to only prostacyclin lowering systemic blood pressure. CONCLUSIONS: Inhaled nitric oxide was a more effective and selective pulmonary vasodilator than prostacyclin and should be considered as the preferred treatment for severe postoperative pulmonary hypertension.

Use of an intraaortic balloon pump as a pneumatic ventricular assist device controller.

Using a circulatory analogue, we investigated sequentially the performance of a dedicated ventricular assist device driver and an intraaortic balloon pump when driving a pneumatic ventricular assist device. Each drive device was compared under identical pumping conditions at rates of 40 to 120 cycles/min against two resistances. Our preliminary study showed that a modified intraaortic balloon pump could drive a pneumatic ventricular assist device as effectively as its dedicated driver. The necessary modifications to and possible further development of the intraaortic balloon in this role are discussed.

Nitric oxide might reduce the need for extracorporeal support in children with critical postoperative pulmonary hypertension.

BACKGROUND: Postoperative pulmonary hypertension is a life-threatening, yet reversible complication of congenital heart operations. Although inhaled nitric oxide (iNO), a selective pulmonary vasodilator, has been shown extensively to improve short-term oxygenation and hemodynamic indices in these patients, its influence on patient outcome has not been evaluated. The purpose of this study was to assess retrospectively whether patients who fulfilled our criteria for extracorporeal life support (ECLS) for critical postoperative pulmonary hypertension still required ECLS after the administration of iNO therapy. METHODS: Since January 1992, 10 patients (age 3 days to 10 months) fulfilled the criteria at our institution for ECLS for postoperative pulmonary hypertension. Of these, 5 could not be separated from cardiopulmonary bypass because of pulmonary hypertension, and 5 had critical pulmonary hypertension (pulmonary arterial pressure approaching systemic arterial pressure) causing severe cardiopulmonary compromise. RESULTS: Six of the 10 ECLS candidates had a sustained response to iNO and survived to discharge from the hospital, without the need for rescue ECLS. Three patients still required ECLS after 30 minutes, 4 hours, and 8 hours of beginning iNO because of failing cardiac output, and 2 survived. The remaining patient died after 5 days of iNO therapy, but was no longer a candidate for ECLS because of sepsis and multiorgan system failure. CONCLUSIONS: Children with critical pulmonary hypertension unresponsive to maximal conventional treatment may be managed successfully with iNO without the need for rescue ECLS. A trial of iNO should therefore be given before the use of ECLS in these patients.

Guidelines for the safe administration of inhaled nitric oxide.

Inhaled nitric oxide (NO) is a selective pulmonary vasodilator, potentially useful in the treatment of pulmonary hypertension and ventilation-perfusion mismatch. High doses of inhaled NO and its oxidative product nitrogen dioxide (NO2) may cause acute lung injury. Using a standard infant ventilator, ventilator circuit and test lung, an administration and monitoring strategy has been defined for inhaled NO and these observations validated in eight ventilated infants. In 90% oxygen, doses of inhaled NO > or = 80 parts per million may result in toxic NO2 concentrations.

A simple laryngoscopic technique for the endotracheal intubation of rabbits.

A safe and reliable technique for the endotracheal intubation of rabbits is described. Direct laryngoscopy is followed by intubation of the trachea with a fine catheter, and subsequent advancement of the endotracheal tube over this catheter.

Risk management protocol for gastrostomy and jejunostomy insertion in ventilator dependent infants.

Gastrostomy, gastrojejunostomy and anti-reflux surgery in infants and children who are chronically ventilator dependent are associated with significant risk of morbidity and mortality. We report outcomes of 22 high risk children who underwent these procedures at our centre. Pre-operative investigations included: overnight oxygen and carbon dioxide monitoring and subsequent optimisation of ventilatory support, echocardiography, video fluoroscopy, and assessment of gastroesophageal reflux. We carried out 24 procedures under general anaesthesia. Twenty-one children used ventilatory support pre-operatively. Median age of first surgical procedure was 18 months (range 3-180). Supplementary feeding was commenced in 20 children prior to procedure, median age 9 months (1-31). Median PICU length of stay was 1 (1-8) days. No children died in the post-operative period. Extubation was possible within 24h in 87% of cases. Complications included; atelectasis (n=2), ileus (n=2), abdominal distension (n=4) and loose stools (n=1). We conclude that, in this high risk cohort of ventilator dependent children with predominantly neuromuscular disorders, with careful assessment, operative intervention can be carried out under general anaesthesia, with the child being extubated early back onto their routine ventilatory support and aggressive airway clearance. Additionally this protocol can minimise post-operative complications and is associated with a good outcome in the majority.

Comparison of oestriol in mother and fetus during labour and in the baby at birth.

The progressive rise in pregnancy of oestriol values and their significance in assessing fetal viability is well known, although the exact function of this increase is not understood. In considering the problem it was thought that further information of oestriol levels in mother, fetus and newborn could prove of value. The mean cord plasma oestriol was lower in small-for-dates than in normal cases, but in both groups it was ten times higher than in the relative maternal peripheral veins. In pooled capillary fetal scalp samples the mean oestriol was slightly higher in normal compared with small-for-dates cases. The use of gas chromatography--mass spectrometry was investigated and shown to give an accurate measurement of plasma oestriol levels. The expense of this procedure may be offset by its ability to determine simultaneously the nature and amount of other steroids present.

Double-blind comparison of the efficacy of extradural diamorphine, extradural phenoperidine and i.m. diamorphine following caesarean section.

A randomized, double-blind study of the efficacy, duration of action and side effects of three analgesic regimens following Caesarean section is described. Patients received i.m. diamorphine 5 mg, extradural phenoperidine 2 mg or extradural diamorphine 5 mg. Analgesia was of rapid onset in all groups, as judged by reductions in linear analogue pain scores and rank pain scores. Time to next analgesia was significantly greater after extradural phenoperidine (5.96 h) and extradural diamorphine (8.39 h) than after i.m. diamorphine (3.40 h) (P less than 0.001). Itching was reported on direct questioning by 50% of patients in the extradural groups. No serious side effects were reported. Factors affecting the disposition of extradurally administered diamorphine are discussed.

Diamorphine analgesia after caesarean section. Comparison of intramuscular and epidural administration of four dose regimens.

In a randomised double-blind study, the efficacy, duration of action and side effects of five diamorphine analgesia regimens following Caesarean section are described. The time to next analgesia was shorter in the 5 mg intramuscular group (3.53 hours) than in any of the four epidural groups: 5 mg (5.7 hours, p = 0.007), 2.5 mg (4.76 hours, p = 0.103), 5 mg with adrenaline 1/200,000 (7.2 hours, p = 0.001) and 2.5 mg with adrenaline 1/200,000 (6.05 hours, p = 0.007). Multiple regression analysis showed that the addition of adrenaline significantly increased the duration of action of epidural diamorphine (p less than 0.05). The 5 mg dose with adrenaline showed no advantage when compared with 2.5 mg with adrenaline (p = 0.16). No serious side effects were reported in any group.

Inhaled nitric oxide for pulmonary hypertension after repair of exomphalos.

Inhaled nitric oxide was used successfully to treat a newborn infant with severe pulmonary hypertension complicating repair of congenital exomphalos. The infant had failed conventional treatment and extracorporeal membrane oxygenation was unsuitable because of the risk of bleeding from the recent laparotomy. Extended treatment with inhaled nitric oxide appears safe and may offer an alternative to mechanical life support in severe cases of neonatal pulmonary hypertension.

Carotid artery pseudoaneurysm as a complication of ECMO.

Any pulsatile neck mass after extracorporeal membrane oxygenation (ECMO) must be viewed as a pseudoaneurysm of the carotid artery until proven otherwise. Prompt diagnosis is necessary utilizing ultrasound. Angiography may not be necessary. Carotid artery pseudoaneurysm requires urgent surgical intervention to prevent catastrophic hemorrhage. The utilization of cardiopulmonary bypass may facilitate safe repair.

Effect of the addition of adrenaline to extradural diamorphine analgesia after caesarean section.

In a randomized double-blind study the effect of the addition of adrenaline to extradural diamorphine was assessed in 54 patients after Caesarean section. Patients received extradural diamorphine 5 mg in saline 10 ml with or without adrenaline 1 in 200,000 for postoperative pain relief. Analgesia was profound and of rapid onset in both groups. Duration of analgesia was greater in the adrenaline group (time to next analgesia 12.51 +/- 0.94 h, mean +/- SEM), than in the saline group (9.87 +/- 0.98 h) (P = 0.057). Analgesia was also more consistent in the adrenaline group, with 77% of patients having more than 8 h of good analgesia compared with 48% in the saline group (P less than 0.05). Plasma morphine concentrations, measured in 12 patients, were lower, although not significantly so, in the adrenaline group and mean time to peak concentration markedly delayed. No serious side effects were observed, but there was a higher incidence of vomiting in the adrenaline group.