Gerfried Zobel

Recombinant Tissue Plasminogen Activator Restores Perfusion in Meningococcal Purpura Fulminans

Objective: To investigate whether an Infusion of recombinant tissue plasminogen activator would dissolve microvascular thromboses and improve organ perfusion in a patient with fulminant meningococcemia. Design: Descriptive case report. Setting: Fifteen-bed pediatric intensive care unit (ICU) in a university hospital. Patient: A 4-month-old male with fulminant meningococcemia, refractory shock, and multiple organ failure. Interventions: In addition to standard aggressive ICU care, the patient received a recombinant tissue plasminogen activator infusion at a total dose of 1.25 mglkg over 4 hrs. Measurements and Main Results: Heart rate, arterial blood pressure, urine output, and base deficit (as a reflection of severity of metabolic acidosis) were recorded immediately before the recombinant tissue plasminogen activator infusion and 4 hrs later, after completion of the recombinant tissue plasminogen activator infusion. The amount of exogenous vasopressor and inotropic support required to maintain the patients hemodynamic status before and after recombinant tissue plasminogen activator infusion were also compared. Subjective observations regarding the patients peripheral perfusion status were also noted. The patient showed a dramatic improvement in hemodynamics, urine output, and metabolic acidosis, as well as a perceived increase in skin perfusion after recombinant tissue plasminogen activator infusion. Conclusions: In this patient, recombinant tissue plasminogen activator infusion resulted in improved organ perfusion and cardiac performance. Selective use of recombinant tissue plasminogen activator in the treatment of fulminant meningococcemia merits further investigation.

Inhaled nitric oxide in patients with critical pulmonary perfusion after fontan-type procedures and bidirectional glenn anastomosis

OBJECTIVE The aim of this study was to evaluate the effects of inhaled nitric oxide in patients with critical pulmonary perfusion after Fontan-type procedures and bidirectional Glenn anastomosis. METHODS Inhaled nitric oxide (mean 4.1 +/- 0.7 ppm, 1.5 to 10 ppm) was administered in 13 patients (mean age 5.6 +/- 1.6 years, 1.5 to 17 years) with critical pulmonary perfusion (central venous pressure > 20 mm Hg or transpulmonary pressure gradient > 10 mm Hg) in the early postoperative period after total cavopulmonary connection (n = 9) or after bidirectional Glenn anastomosis (n = 4). RESULTS In patients after total cavopulmonary connection inhaled nitric oxide therapy decreased central venous pressure by 15.3% +/- 1.4% (p = 0.0001) and transpulmonary pressure gradient by 42% +/- 8% (p = 0.0008) and increased mean systemic arterial and left atrial pressures by 12% +/- 3.6% (p = 0.011) and 28% +/- 8% (p = 0.007), respectively. Arterial and venous oxygen saturations improved by 8.2% +/- 1% (p = 0.005) and 14% +/- 4.3% (p = 0.03), respectively. In patients after bidirectional Glenn anastomosis inhaled nitric oxide therapy resulted in a decrease of central venous pressure by 22% +/- 1% and of the transpulmonary pressure gradient by 55% +/- 6% and improved arterial and venous oxygen saturations by 37% +/- 29% and 11% +/- 3%, respectively. Mean systemic arterial and left atrial pressures remained nearly unchanged. No toxic side effect was observed in any patient. CONCLUSION Inhaled nitric oxide may play an important role in the management of transient critical pulmonary perfusion caused by reactive elevated pulmonary vascular resistance in the early postoperative period after Fontan-type operations and bidirectional Glenn anastomosis.

Activation of the clotting system during extracorporeal membrane oxygenation in term newborn infants

OBJECTIVES To determine the degree of clotting activation that occurs with the usual anticoagulation regimen with systemic heparinization. METHODS To allow a standardized comparison of the patients, this study focused on the first 48 hours of extracorporeal membrane oxygenation (ECMO) in term newborn infants. The ECMO perfusion circuit consisted of a roller pump, silicone membrane lungs, and silicone rubber tubing. Coagulation was controlled routinely by measuring prothrombin time, fibrinogen, antithrombin III, and reptilase time. Platelet counts, activated clotting time, and heparin concentration were controlled regularly. The following specific activation markers of the clotting system were measured: prothrombin activation fragment 1 + 2(F1+2), thrombin-antithrombin III complexes, and D-dimer. Measurements were done before the start of ECMO, after 5 minutes, and at hours 1, 2, 3, 4, 6, 12, 24 and 48. RESULTS All seven term infants had excessively high levels of clotting activation markers within the first 2 hours of ECMO: F1+2, 11.6(+/- O.9) nmol/L (mean +/- SEM); thrombin-antithrombin, 920(+/- 2.2) microg/L; D-dimer, 15.522(+/- 3.689) ng/L. During the next 46 hours of ECMO, F1+2 and thrombin-antithrombin III complexes decreased from those high values, whereas D-dimer did not. The increase of activation markers was accompanied by low fibrinogen, low platelet counts. and prolongation of reptilase time. CONCLUSIONS These findings fit the pattern of consumptive coagulopathy during neonatal ECMO, especially in the first 24 hours.

Tissue plasminogen activator (alteplase) treatment for femoral artery thrombosis after cardiac catheterisation in infants and children.

OBJECTIVE--To determine the efficacy of fibrinolytic therapy with tissue plasminogen activator (alteplase) in infants and children with arterial thrombosis after cardiac catheterisation. DESIGN--Use of alteplase (Actilyse) in a protocol with prospective data collection. Alteplase was administered to infants and children with arterial thrombosis after cardiac catheterisation. A dose of 0.5 mg/kg/h was given continuously via a peripheral vein for the first hour followed by 0.25 mg/kg/h till clot lysis occurred or treatment had to be stopped because of bleeding complications. SETTING--University hospital, intensive care unit. PATIENTS--17 consecutive infants and children with femoral artery thrombosis after cardiac catheterisation between 1 April 1988 and 31 October 1991. MAIN OUTCOME MEASURE--Reopening of the vessel. RESULTS--Complete clot lysis was achieved in 16 of 17 patients within 4-11 hours after the start of treatment. In one patient only partial lysis occurred. After complete lysis rethrombosis developed in one patient 15 hours after the end of treatment. Bleeding complications were seen in nine patients. These were restricted to the arterial puncture site, except for one who showed mild epistaxis. Three patients had to be treated with packed erythrocytes. CONCLUSIONS--Alteplase was an effective treatment of arterial thrombosis after cardiac catheterisation in infants and children. Further studies are needed to determine whether lower doses will reduce the frequently observed bleeding complications.

Inhaled Nitric Oxide versus Inhaled Prostacyclin and Intravenous versus Inhaled Prostacyclin in Acute Respiratory Failure with Pulmonary Hypertension in Piglets

ABSTRACT: This study was a prospective, randomized design to compare oxygenation and pulmonary hemodynamics between inhaled nitric oxide (NO) and inhaled prostacylcin (PGI2), and between inhaled and i.v. PGI2 in acute respiratory failure with pulmonary hypertension. Acute respiratory failure with pulmonary hypertension was induced in 12 piglets weighing 9–12 kg by repeated lung lavages and a continuous infusion of the stable endoperoxane analogue of thromboxane. Thereafter the animals were randomly assigned either for NO or PGI2 application. All animals were treated with different concentrations of NO or different doses of PGI2 applied i.v. and inhaled in random order. Continuous monitoring included ECG, central venous pressure (CVP), mean pulmonary artery pressure (MPAP), mean arterial pressure (MAP), artertial oxygen saturation (SaO2), and mixed venous oxygen saturation (SvO2) measurements. NO inhalation of 10 ppm resulted in a significant increase in Pao2/fraction of inspired oxygen (FiO2) from 7.8 ± 1.34 kPa to 46.1 ± 9.7 kPa. MPAP decreased significantly from 5.1 ± 0.26 kPa to 3.7 ± 0.26 kPa during inhaled NO of 40 ppm; i.v. infusion of PGI2 slightly increased oxygenation parameters. A significant increase in Pao2/FiO2 up to 32.4 ± 3.1kPa was observed during PGI2 aerosol delivery (p < 0.01); i.v. PGI2 decreased MAP from 11.5 ± 0.39 kPa to 9.8 ± 0.66 kPa (p < 0.05) and MPAP from 5.8 ± 0.53 kPa to 4.5 ± 0.66 kPa, respectively (p < 0.05). PGI2 aerosol delivery significantly decreased the MPAP to 3.7 ± 0.53 kPa (p < 0.05) without influencing the MAP. It was concluded that inhaled NO and inhaled PGI2 act as selective pulmonary vasodilators in acute respiratory failure with pulmonary hypertension resulting in improved oxygenation mainly due to improved mismatch of pulmonary perfusion and ventilation. Intravenous PGI2 improves oxygenation and pulmonary hemodynamics to a lesser extent than aerosolized PGI2 and has the risk of systemic hypotension at a higher dose.

Inhibitor to factor V after exposure to fibrin sealant during cardiac surgery in a two‐year‐old child

Muntean W, Zenz W, Finding K, Zobel G, Beitzke A. Inhibitor to factor V after exposure to fibrin sealant during cardiac surgery in a two‐year‐old child. Acta Prediatr 1994;83:84–7. Stockholm. ISSN 0803–5253

Reduction of colonization and infection rate during pediatric intensive care by selective decontamination of the digestive tract.

ObjectiveTo compare the effects of two different antibiotic regimes on the colonization and infection rates of critically ill pediatric patients. DesignA prospective randomized trial. SettingA pediatric ICU in a university hospital. PatientsFifty critically ill pediatric patients who required intensive care for at least 4 days were randomly allocated to either the selective parenteral and enterai antisepsis regimen (treatment group, n = 25) or the control group (n = 25). InterventionsThe treatment group received oral nonabsorbable antimicrobial agents (polymyxin E, gentamicin, and amphotericin B) and parenteral cefotaxime, whereas the control group received either perioperative antibiotic prophylaxis or antibiotic therapy according to clinical or microbiological evidence of infection. ResultsBoth groups were comparable for age, body weight, sex, and severity of illness. Colonization with Gram-negative microorganisms and yeasts in the oropharynx, and digestive and respiratory tracts increased rapidly up to 52% in the control group, whereas there was no colonization with these microorganisms in the treatment group. The occurrence rates of acquired secondary infections in the control and treatment groups were 36% and 8%, respectively (p < .025). There were no differences between groups in the duration of intensive care or mortality rate. ConclusionSelective oropharyngeal and gastrointestinal decontamination combined with systemic cefotaxime application allows for a significant reduction of the colonization rate with Gram-negative bacteria and yeasts in critically ill pediatric patients undergoing prolonged intensive care. In addition, it significantly reduces the Gram-negative infection rate of the respiratory system. However, this therapeutic approach does not alter ICU length of stay or mortality rate.

Congenital central hypoventilation syndrome (Ondine's curse syndrome) in two siblings: Delayed diagnosis and successful noninvasive treatment

Congenital central hypoventilation syndrome (CCHS, Ondines curse syndrome) is a rare respiratory disorder; less than 100 cases have been reported. Familiality of the disease has been discussed, but only few familial cases have been reported so far. In this report we describe the occurrence of CCHS in two male siblings. Diagnosis was established only at the age of 4 years in the first case, although the patient had disease related symptoms since early infancy. The second patient was one of dizygotic twins, he was diagnosed with CCHS at the age of 8 months. Up to that age only moderate desaturations had been observed. The other twin was unaffected by the disease. Both patients were successfully treated by nocturnal positive-pressure ventilation via a specially adapted face mask. They show satisfactory physical and neurologic development.

Five years experience with continuous extracorporeal renal support in paediatric intensive care

Continuous arterio-venous haemofiltration (CAVH) and continuous veno-venous haemofiltration (CVVH) were used as renal support in 52 critically ill infants and children with acute renal failure. The majority of the patients were on mechanical ventilation (90%) and needed vasopressor support (85%). Uraemia was satisfactorily controlled with both treatment modes. Post-treatment serum urea levels were not different between survivors (94±8.8 mg/dl) and non-survivors (99.5±8.8 mg/dl). There were significant differences between survivors and non-survivors in the mean arterial pressure (64.7±3.8 vs 48.0±2.2 mmHg,p<0.001), the number of organ system failures (2.9±0.16 vs 3.8±0.21,p<0.025), and the severity of illness assessed by the acute physiologic score for children (APSC 19.4±1.9 vs 26.3±1.9,p<0.01). The overall mortality was 48%. The mortality in the CVVH group (65%) was higher than in the CAVH group (40%). Death was significantly related to sepsis (p<0.005) and multiple system organ failure (p<0.005). A major complication during CAVH was one femoral artery thrombosis after 12 days of treatment. Technical problems were only observed during CVVH. CAVH and CVVH are safe and effective methods of continuous renal support for critically ill paediatric patients with multiple system organ failure. CAVH is simpler, needs no specially trained staff and seems to the ideal renal replacement system for critically ill infants.

Tick-borne encephalitis in a 3-month-old child

Tick-borne encephalitis has not been reported in infants younger than 12 months of age. We report a 3.5-month-old child with a serologically proven tick-borne encephalitis. The infant had a history of a tick bite 3.5 weeks before the first symptoms of encephalitis appeared. The family lives in an endemic area of the disease. There were no prodromal signs and the course of the disease was monophasic. In an endemic area, prophylactic treatment with hyperimmunoglobulin after a tick bite should be considered even in very young infants, but in most children active immunization is probably not necessary because of infrequent exposure. Acitve immunization is still recommended after the 1st year of life.