Prolonged arterial hypotension due to propofol used for endotracheal intubation in a newborn infant

Prolonged arterial hypotension due to propofol used for endotracheal intubation in a newborn infant

Case presentation
During early pregnancy, the newborn’s mother had had malaria with hemolytic crisis but had recovered well under antimalarial treatment in Africa. Subsequent prenatal care in Switzerland revealed normalisation of pregnancy. At a gestational age of 37 4/7 weeks, an elective cesarean section (spinal anesthesia) was performed because of breech presentation. Apgar scores were 2 and 4 at 1 and 5 minutes, respectively, mainly due to poor respiratory effort. The newborn male infant was quickly intubated without medication. On transport to the regional hospital, there was accidental extubation. After arrival at the hospital, the cyanotic and apneic newborn received 8mg/kg propofol, 10 mcg/kg fentanyl and muscle relaxation and was reintubated.

On arrival at our neonatal critical care unit, the patient was deeply sedated with small pupils, spontaneous hypoventilation and with motor reaction only to painful stimulation. Birth weight, body length and head circumference were within normal range for age. In addition, there was arterial hypotension (MABP 25-30 mmHg), which was treated with volume 20ml/kg and dopamine 5 mcg/kg/min over 24 hours. His cardiovascular status remained otherwise completely normal. The patient was weaned from the ventilator within another 24 hours and showed no respiratory distress (FiO2 of 0.21 since admission). He never showed any signs of a systemic inflammatory response syndrome or of infection. Chest x-rays, head ultrasound and laboratory examinations (hemoglobin, leucocytes, electrolytes, renal function and plasmodium falciparum antigen) remained normal, except for a positive Coombs test due to AO-incompatibility. He went home at the age of 6 days with a normal neurologic and cardiopulmonary status.

Discussion

The etiology of the infant’s poor respiratory effort immediately after birth remains unclear. The newborn might have suffered from side effects of maternal anesthesia. Neonatal encephalopathy due to maternal infection may present with bradypnea, but we would expect prolonged hypoventilation and additional signs of neonatal encephalopathy.

Prolonged arterial hypotension seen after the second endotracheal intubation however is most probably due to the medications used for intubation. Arterial hypotension seen after a single bolus of propofol is probably due to overdosing (maximal recommended dose is 3mg/kg bodyweight), limited hepatic clearance in the newborn infant, and fentanyl induced increase in propofol serum concentration.

Considering the increasing popularity of propofol (Disoprivan®) use in neonatal and pediatric anesthesia, it is important to remember the following facts:

1) The “propofol-infusion syndrome” does exist: it is rare but has a high fatality rate; propofol should therefore not be used for longtime sedation in neonatal or pediatric intensive care.

2) A single bolus of propofol reduces myocardial contractility and systemic vascular resistance (similar to thiopenthal). There is an increase in right-to-left shunting through fetal channels with worsening of cyanosis and pulmonary hypertension . Propofol should therefore not be used for intubation or sedation in conditions associated with cardiopulmonary compromise, such as newborns with respiratory distress syndrome, pulmonary hypertension, sepsis, cardiomyopathy or congenital heart disease. In these patients other medications for intubation have been shown to be much safer, such as ketamine or lowe dose benzodiazepines.

3) Recent studies suggest that there is propofol-related neurotoxicity.
In conclusion, despite the current unhibited enthusiasm for propofol, there are well documented and potentially lethal side-effects of propofol. This requires a differentiated approach to the use of propofol. Especially in the newborn infant, there is no place for propofol.

Congenital Cutaneous Candidiasis

Congenital cutaneous candidiasis (CCC): a rare skin disorder of the neonate


IntroductionCutaneous congenital candidiasis (CCC) is a rare disease of the term or premature infant consisting of a typical generalized eruption (maculae, papules, or pustules) at birth, usually without other signs or symptoms. CCC is always secondary to Candida chorioamnionitis. Despite the high frequency of vulvo-vaginitis in pregnant women the condition is very rare with at most some hundred cases described in the literature. However, as the condition is essentially benign and self-limited, underdiagnosis is likely. We present two cases of CCC, discuss the diagnostic features and proposed treatments.

Case presentations
Case 1:
A female infant of 3270 g (P 50-90) was delivered by caesarean section at 38 weeks of gestation after an uneventful pregnancy except for vaginal candidiasis at 26 weeks of gestation treated locally (cotrimoxazole). Membranes ruptured seven hours before birth and amoxicillin/gentamycin was administered during labour for maternal fever. The presence of disseminated white granulomas was noted on the umbilical cord. Adaptation was perfect with Apgar scores of 9, 10 and 10. A red maculo-papular rash (Fig. 1, 2) covering the whole body and sparing only the palms, soles and mucous membranes was noted at birth. Physical examination was otherwise normal except for mild tachypnea (60 to 80 breaths per minute) on day one with a normal chest x-ray. Total leukocyte count was 11.0 G/L with 52.5 % polymorphonuclear and 11.5% band forms. Bacteriology of the placenta grew yeast and umbilical cord histology revealed the presence of mycotic abscesses (Fig. 3-5). Mannan antigens were positive and antibodies remained negative. A 7-day-course of oral fluconazole (5 mg/kg/d) was started on day two for presumed congenital cutaneous candidiasis. Candida albicans grew on the placental swabs and neonatal gastric aspirations. Blood cultures remained negative for bacteria and fungi. The rash became slightly squamous over the next days and disappeared completely by the end of the first week of life.

Case 2:
A male infant of 2450 g (P 50-90) was born by normal vaginal delivery at 34 weeks of gestation despite tocolytics. Membranes ruptured 10 minutes before delivery. Apgar scores were 6, 7 and 9. The child presented at birth with a disseminated red maculo-papular rash, predominant on the trunk and head. White granulomas were noted on the umbilical cord. Amoxicillin/gentamycin and acyclovir were started immediately despite an unremarkable physical examination with the exception of the rash. Total leukocyte count was 21.5 G/L with 54% polymorphonuclear and 3% band form. Herpes simplex PCR was negative in cerebrospinal fluid and skin specimen.

Candida albicans grew on placental swabs and on neonatal skin swabs as well as in gastric aspirates and urine. Antibiotics and acyclovir were therefore stopped on day 4 based on the diagnosis of CCC and a 7-day-course of oral fluconazole was started. Blood cultures remained negative for bacteria and fungi. After a phase of desquamation (Fig. 6), the rash progressively disappeared over one week.

Discussion

Cutaneous congenital candidiasis (CCC) always appears to be acquired in utero by ascending infection contrasting with neonatal candidiasis, acquired either at birth by an infected birth canal or postnatally. For infants weighing less than 1000 g, contraceptive intrauterine devices and cervical cerclage have been described to increase the risk for CCC, whereas in neonates over 1000 g this association has not been shown. Premature infants under 1000 g also have the greatest risk of invasive disease due to their immature immune system and compromised muco-cutaneous barrier.

The initial finding may be a generalized or patchy erythema but typically the rash consists of generalized maculo-papular and/or pustulous eruptions with lesions 2 to 4 mm in diameter (Fig 1). CCC is reported more commonly in the full-term infant (1), where it usually has a self-limited and benign course, despite the obligatory presence of Candida species chorio-amnionitis and funiculitis.

Although there is no proven benefit of any antifungal therapy, some authors recommend topical and oral antimycotics to reduce the risk of systemic spread. Indeed, in the VLBW infant, colonization is generally accepted to always preceed invasive disease (1,2). We opted to treat our patients with the well tolerated oral antimycotic fluconazole, and would particularly recommend do so in the VLBW infant.
Due to the relatively low sensitivity and long delay of blood cultures for yeasts, more recent tests focus on structural membranes of Candida by enzyme immunoassay of mannan antigens and antibodies. The recent generation detection tests are considered of moderate sensitivity but good specificity (4, 6) and may precede blood culture results. Positive antigen and negative antibody may suggest early systemic infection in our first case. Whether such a test may predict beginning systemic infection of the neonate with CCC remains to be proven as no follow-up serology was performed.

Differential diagnosis of CCC

is extensive and should initially include Listeria monocytogenes infection, Staphylococcal pustulosis, impetigo, Herpes group infection, syphilis and epidermolysis bullosa. However, the diagnosis can rapidly be confirmed on microscopy by the presence of Candida albicans spores in skin scrapings, which, after a longer delay, will also result in positive cultures. Candida chorio-amnionitis or funiculitis is an obligatory finding and placental swabs and pathology is essential. By definition, in CCC Candida is confined to the epithelium and gastrointestinal tract. Blood cultures, cerebrospinal fluid and urine remain sterile.

Summary

CCC is a rare disease of the neonate caused by Candida species land acquired in utero. Chorio-amnionitis is therefore mandatory and diagnosis requires microbiological or histological demonstration. The major risk factors are the presence of intrauterine devices during pregnancy and cervical cerclage. Diagnosis of CCC allows reassurance of the parents, as the disease is benign and exempt of long-term sequels. As the disease is self-limited and mostly benign, it may be more common than reported in the literature. Oral or systemic antifungal treatment is debated but should be considered particularly for the VLBW infant, at high risk of invasive disease.

Prrolonged arterial hypotension due to propofol used for endotrachial intubation in a newborn infant

Prolonged arterial hypotension due to propofol used for endotracheal intubation in a newborn infant

Case presentation
During early pregnancy, the newborn’s mother had had malaria with hemolytic crisis but had recovered well under antimalarial treatment in Africa. Subsequent prenatal care in Switzerland revealed normalisation of pregnancy. At a gestational age of 37 4/7 weeks, an elective cesarean section (spinal anesthesia) was performed because of breech presentation. Apgar scores were 2 and 4 at 1 and 5 minutes, respectively, mainly due to poor respiratory effort. The newborn male infant was quickly intubated without medication. On transport to the regional hospital, there was accidental extubation. After arrival at the hospital, the cyanotic and apneic newborn received 8mg/kg propofol, 10 mcg/kg fentanyl and muscle relaxation and was reintubated.

On arrival at our neonatal critical care unit, the patient was deeply sedated with small pupils, spontaneous hypoventilation and with motor reaction only to painful stimulation. Birth weight, body length and head circumference were within normal range for age. In addition, there was arterial hypotension (MABP 25-30 mmHg), which was treated with volume 20ml/kg and dopamine 5 mcg/kg/min over 24 hours. His cardiovascular status remained otherwise completely normal. The patient was weaned from the ventilator within another 24 hours and showed no respiratory distress (FiO2 of 0.21 since admission). He never showed any signs of a systemic inflammatory response syndrome or of infection. Chest x-rays, head ultrasound and laboratory examinations (hemoglobin, leucocytes, electrolytes, renal function and plasmodium falciparum antigen) remained normal, except for a positive Coombs test due to AO-incompatibility. He went home at the age of 6 days with a normal neurologic and cardiopulmonary status.
DiscussionThe etiology of the infant’s poor respiratory effort immediately after birth remains unclear. The newborn might have suffered from side effects of maternal anesthesia. Neonatal encephalopathy due to maternal infection may present with bradypnea, but we would expect prolonged hypoventilation and additional signs of neonatal encephalopathy.

Prolonged arterial hypotension seen after the second endotracheal intubation however is most probably due to the medications used for intubation. Arterial hypotension seen after a single bolus of propofol is probably due to overdosing (maximal recommended dose is 3mg/kg bodyweight), limited hepatic clearance in the newborn infant, and fentanyl induced increase in propofol serum concentration (1-3).

Considering the increasing popularity of propofol (Disoprivan®) use in neonatal and pediatric anesthesia, it is important to remember the following facts:

1) The “propofol-infusion syndrome” does exist: it is rare but has a high fatality rate; propofol should therefore not be used for longtime sedation in neonatal or pediatric intensive care (4).

2) A single bolus of propofol reduces myocardial contractility and systemic vascular resistance (similar to thiopenthal). There is an increase in right-to-left shunting through fetal channels with worsening of cyanosis and pulmonary hypertension (5-8). Propofol should therefore not be used for intubation or sedation in conditions associated with cardiopulmonary compromise, such as newborns with respiratory distress syndrome, pulmonary hypertension, sepsis, cardiomyopathy or congenital heart disease. In these patients other medications for intubation have been shown to be much safer, such as ketamine or lowe dose benzodiazepines.

3) Recent studies suggest that there is propofol-related neurotoxicity (9-11).

In conclusion

despite the current unhibited enthusiasm for propofol, there are well documented and potentially lethal side-effects of propofol. This requires a differentiated approach to the use of propofol. Especially in the newborn infant, there is no place for propofol.

Heart failure caused by propranolol treatment in a newborn infant

Heart failure caused by propranolol treatment in a newborn infant

Case report

Supraventricular tachycardia developed at 34 weeks of gestation after an uneventful pregnancy. Fetal echocardiogram showed a structurally normal heart and an optically normal ventricular function. There were no signs of hydrops except for minimal pericardial and pleural effusions. The mother was started on digoxin with conversion of the tachycardia into a normal sinus rhythm. The digoxin therapy was continued until delivery.
A baby boy was delivered by cesarean section at 38 weeks of gestation with an Apgar score of 8-8-8 and a birthweight of 3150g (P 25-50). The baby was in sinus rhythm with a heart rate of 120 to 130 per minute. He developed respiratory distress and was admitted to the neonatal unit with Fi02 of 60%. At the time of admission he was tachypnoeic (80 per minute), had sternal retractions, nasal flaring and grunting. Chest X-ray showed a cardiothoracic index of 0.55 and hyperinflated lungs compatible with wet lungs. The baby improved rapidly and supplemental oxygen was reduced to 25% by the end of the first day of life. Digoxin measurement in cord blood (0.5nmol/l) was below the therapeutic level.
On the first day of life cardiac assessment was performed. Auscultation of the heart was totally normal. ECG (figure) showed a normal sinus rhythm with a heart rate of 130-140 per minute, tall P waves suggesting atrial hypertrophy, and no evidence of Wolff-Parkinson-White syndrome; echocardiography showed a 2mm persistent arterial duct with bidirectional shunting confirming pulmonary hypertension, patent foramen ovale with left-to-right shunt, and otherwise a structurally normal heart. Both atria were enlarged. The measurement of systolic ventricular function was normal but there was a mild diastolic dysfunction and the ventricular filling appeared to be slightly impaired.

After evaluation of the situation with the paediatric cardiologists it was decided to put the baby on propranolol, which was started on the first day of life at a dose of 1mg/kg/day and increased gradually up to 3mg/kg/day on day three. The baby never showed supraventricular tachycardia but his heart rate slowed to about 90-100 per minute. Further, the baby was extremely quiet and showed very poor feeding.
Following the initial improvement on the first day of life, the baby deteriorated steadily and developed signs of heart failure. On the fourth day of life he presented suddenly with marked tachypnoea of 120 per minute. He was hypercapneic, required 40% of supplemental oxygen and was placed on nasal CPAP. In addition he had several episodes of apnoea and bradycardia. Further examination revealed a pale infant with diminished peripheral perfusion; clinical signs of right-sided heart failure like edema, puffy eyelids, or enlargement of the liver were absent. Heart auscultation was still normal without gallop rhythm; blood pressure was normal. ECG was not performed at this stage, on chest X-ray there was cardiomegaly (cardiothoracic index 0.65) and signs of pulmonary venous congestion. Echocardiography showed cardiomegaly with ventricular and atrial dilatation and a mild reduced ventricular contractility; the arterial duct had closed spontaneously. Our hypothesis was that the heart failure was the consequence of propranolol treatment. The drug was discontinued and a low dose of diuretics was given. The baby improved rapidly and supplemental oxygen as well as nasal CPAP could be stopped within 12 hours. He started to feed and was increasingly active. The diuretics were stopped after 2 days of treatment. The antibiotics started at the time of clinical deterioration were stopped after obtaining negative blood cultures. On control echocardiography at the age of seven days the systolic ventricular function was normal. Propranolol was restarted at the age of ten days begining with a small dose of 0.5mg/kg/d and was increased daily. This time it was well tolerated without development of heart failure. Holter ECG was normal and the baby was discharged from hospital at the age of 15 days. Ambulatory follow up at the paediatric cardiology unit showed an uneventful course with no further episodes of tachycardia.

Discussion

Intrauterine supraventricular tachycardia can lead to heart failure and hydrops within a short time and therefore requires rapid treatment. Among the many possibilities of prenatal treatment digoxin given to the mother is often the first choice and was successful in the present case with rapid conversion into sinus rhythm.
It is nowadays well established that newborns having had fetal supraventricular tachycardia in utero should be treated prophylactically during the first year of life. Beta blockers are popular drugs and propranolol is usually used as the first line of treatment because it is easily applicable, usually well tolerated, and has a low incidence of complications. Side effects are described, among them the negative inotropic and chronotropic effect of the beta blockers which can accentuate heart failure. Other side effects are bradycardia and other arrhythmias, arterial hypotension, diminished peripheral perfusion, apneic episodes, bronchospasms, allergic skin reactions, and reduced activity.
Our patient presented postnatally with sinus rhythm and a normal systolic function on echocardiogram. Despite the normal shortening fraction, ejection fraction and cardiac output, echocardiogram showed diastolic dysfunction which led to the suspicion of mild heart failure during the tachypnoeic epidose. In this patient the measurement of cardiac function was normal but the cardiac reserve was poor and this was underestimated. Furthermore, the baby had respiratory distress after birth, which accentuated his cardiac overload. Propranolol was started at that stage and this led to a deterioration of the cardiac function within four days as well as to pulmonary hypercirculation and edema. The negative chronotropic and inotropic effect of propranolol accentuated the reduction of cardiac output and led to congestive heart failure, which could not be compensated by an elevation of the heart rate as this adrenergic response was blocked by propranolol. Heart failure was however limited to the left side in this case and it is unclear why right-sided failure was not observed.

Conclusion

Propranolol is an effective drug and is usually well tolerated. However caution is required in the case of a poor cardiac reserve or in conditions which may produce cardiac overload, for example, respiratory distress in the newborn. If this is the case, another antiarrhythmic drug or delay in starting the treatment should be considered.