Dick G. Markhorst

Diffuse neonatal haemangiomatosis: new views on diagnostic criteria and prognosis

Diffuse neonatal haemangiomatosis (DNH) is a rare and life‐threatening congenital disorder. An extensive retrospective analysis of the literature was performed to evaluate the clinical features, therapies and prognostic factors of DNH. Reports on 68 patients with DNH were obtained. The skin, liver, lungs, brain and intestine were the organs most commonly involved. Congestive heart failure (CHF) was the primary cause of death. The mortality rate was 77.4% in untreated patients and 27% in treated patients. CHF, Kasabach‐Merritt syndrome (KMS) and the involvement of five or more organs were important risk factors in DNH. The measurement of cardiac output might give more insight into the potential prognostic value of total blood‐volume loss through shunting in the haemangiomas. Reports on 64 patients with neonatal haemangiomatosis limited to only the skin and liver were also obtained. The clinical features and outcome of patients with only cutaneous and hepatic haemangiomas were similar to those of patients with DNH. The inclusion criteria for DNH should be expanded to include similar patients with only cutaneous and hepatic haemangiomas.

Imposed work of breathing during high-frequency oscillatory ventilation: a bench study

IntroductionThe ventilator and the endotracheal tube impose additional workload in mechanically ventilated patients breathing spontaneously. The total work of breathing (WOB) includes elastic and resistive work. In a bench test we assessed the imposed WOB using 3100 A/3100 B SensorMedics high-frequency oscillatory ventilators.MethodsA computer-controlled piston-driven test lung was used to simulate a spontaneously breathing patient. The test lung was connected to a high-frequency oscillatory ventilation (HFOV) ventilator by an endotracheal tube. The inspiratory and expiratory airway flows and pressures at various places were sampled. The spontaneous breath rate and volume, tube size and ventilator settings were simulated as representative of the newborn to adult range. The fresh gas flow rate was set at a low and a high level. The imposed WOB was calculated using the Campbell diagram.ResultsIn the simulations for newborns (assumed body weight 3.5 kg) and infants (assumed body weight 10 kg) the imposed WOB (mean ± standard deviation) was 0.22 ± 0.07 and 0.87 ± 0.25 J/l, respectively. Comparison of the imposed WOB in low and high fresh gas flow rate measurements yielded values of 1.63 ± 0.32 and 0.96 ± 0.24 J/l (P = 0.01) in small children (assumed body weight 25 kg), of 1.81 ± 0.30 and 1.10 ± 0.27 J/l (P < 0.001) in large children (assumed body weight 40 kg), and of 1.95 ± 0.31 and 1.12 ± 0.34 J/l (P < 0.01) in adults (assumed body weight 70 kg). High peak inspiratory flow and low fresh gas flow rate significantly increased the imposed WOB. Mean airway pressure in the breathing circuit decreased dramatically during spontaneous breathing, most markedly at the low fresh gas flow rate. This led to ventilator shut-off when the inspiratory flow exceeded the fresh gas flow.ConclusionSpontaneous breathing during HFOV resulted in considerable imposed WOB in pediatric and adult simulations, explaining the discomfort seen in those patients breathing spontaneously during HFOV. The level of imposed WOB was lower in the newborn and infant simulations, explaining why these patients tolerate spontaneous breathing during HFOV well. A high fresh gas flow rate reduced the imposed WOB. These findings suggest the need for a demand flow system based on patient need allowing spontaneous breathing during HFOV.

High-frequency oscillatory ventilation in children: a single-center experience of 53 cases.

IntroductionThe present article reports our experience with high-frequency oscillatory ventilation (HFOV) in pediatric patients who deteriorated on conventional mechanical ventilation.MethodsThe chart records of 53 consecutively HFOV-treated patients from 1 January 1998 to 1 April 2004 were retrospectively analyzed. The parameters of demographic data, cause of respiratory insufficiency, Pediatric Index of Mortality score, oxygenation index and PaCO2 were recorded and calculated at various time points before and after the start of HFOV, along with patient outcome and cause of death.ResultsThe overall survival rate was 64%. We observed remarkable differences in outcome depending on the cause of respiratory insufficiency; survival was 56% in patients with diffuse alveolar disease (DAD) and was 88% in patients with small airway disease (SAD). The oxygenation index was significantly higher before and during HFOV in DAD patients than in SAD patients. The PaCO2 prior to HFOV was higher in SAD patients compared with DAD patients and returned to normal values after the initiation of HFOV.ConclusionHFOV rescue therapy was associated with a high survival percentage in a selected group of children. Patients with DAD primarily had oxygenation failure. Future studies are necessary to evaluate whether the outcome in this group of patients may be improved if HFOV is applied earlier in the course of disease. Patients with SAD primarily had severe hypercapnia and HFOV therapy was very effective in achieving adequate ventilation.

Effect of acute renal failure on outcome in children with severe septic shock

Acute renal failure (ARF) requiring renal replacement therapy (RRT) has been associated with an excess risk of mortality in adult patients with septic shock, but it is unknown whether this is also applicable to pediatric patients. We therefore conducted a retrospective pilot study. All children presenting with septic shock between 1st January 1998 and 1st April 2004 were analyzed. Patients with fluid refractory-dopamine resistant shock, necessitating the use of noradrenaline, were included. ARF was defined as the deterioration of renal function to the extent that renal replacement therapy was required (ARF group). This ARF group was compared with patients without ARF (non-ARF group). Out of the 22 children with severe septic shock, seven developed ARF. PIM2 and PRISM scores upon admission were comparable between both groups. Mortality rates were significantly higher in patients with ARF (57.1% vs 6.7%; p=0.02). Pediatric patients with severe septic shock developing ARF have excess mortality compared to pediatric patients who do not develop ARF, although on diagnosis, severity of underlying disease and calculated risk of mortality were comparable. A multicenter trial is necessary to confirm these findings and to determine the contribution of ARF to pediatric sepsis mortality.

Tidal Volume and Mortality in Mechanically Ventilated Children: A Systematic Review and Meta-Analysis of Observational Studies

Objective:To determine whether tidal volume is associated with mortality in critically ill, mechanically ventilated children. Data Sources:MEDLINE, EMBASE, and CINAHL databases from inception until July 2013 and bibliographies of included studies without language restrictions. Study Selection:Randomized clinical trials and observational studies reporting mortality in mechanically ventilated PICU patients. Data Extraction:Two authors independently selected studies and extracted data on study methodology, quality, and patient outcomes. Meta-analyses were performed using the Mantel-Haenszel random-effects model. Heterogeneity was quantified using I2. Study quality was assessed using the Newcastle-Ottawa Score for cohort studies. Data Synthesis:Out of 142 citations, seven studies met the inclusion criteria, and additional two articles were identified from references of the found articles. One was excluded. These eight studies included 1,756 patients. Mortality rates ranged from 13% to 42%. There was no association between tidal volume and mortality when tidal volume was dichotomized at 7, 8, 10, or 12 mL/kg. Comparing patients ventilated with tidal volume less than 7 mL/kg and greater than 10 mL/kg or greater than 12 mL/kg and tidal volume less than 8 mL/kg and greater than 10 mL/kg or greater than 12 mL/kg also showed no association between tidal volume and mortality. Limiting the analysis to patients with acute lung injury/acute respiratory distress syndrome did not change these results. Heterogeneity was observed in all pooled analyses. Conclusions:A relationship between tidal volume and mortality in mechanically ventilated children could not be identified, irrespective of the severity of disease. The significant heterogeneity observed in the pooled analyses necessitates future studies in well-defined patient populations to understand the effects of tidal volume on patient outcome.

Reflections on Pediatric High-Frequency Oscillatory Ventilation From a Physiologic Perspective

Mechanical ventilation using low tidal volumes has become universally accepted to prevent ventilator-induced lung injury. High-frequency oscillatory ventilation (HFOV) allows pulmonary gas exchange using very small tidal volume (1–2 mL/kg) with concomitant decreased risk of atelectrauma. However, its use in pediatric critical care varies between only 3% and 30% of all ventilated children. This might be explained by the fact that the beneficial effect of HFOV on patient outcome has not been ascertained. Alternatively, in contrast with present recommendations, one can ask if HFOV has been employed in its most optimal fashion related especially to the indications for and timing of HFOV, as well as to using the best oscillator settings. The first was addressed in one small randomized study showing that early use of HFOV, instead of rescue use, was associated with improved survival. From a physiologic perspective, the oscillator settings could be refined. Lung volume is the main determinant of oxygenation in diffuse alveolar disease, suggesting using an open-lung strategy by recruitment maneuvers, although this is in practice not custom. Using such an approach, the patient can be oscillated on the deflation limb of the pressure-volume (P-V) curve, allowing less pressure required to maintain a certain amount of lung volume. Gas exchange is determined by the frequency and the oscillatory power setting, controlling the magnitude of the membrane displacement. Experimental work as well as preliminary human data have shown that it is possible to achieve the smallest tidal volume with concomitant adequate gas exchange when oscillating at high frequency and high fixed power setting. Future studies are needed to validate these novel approaches and to evaluate their effect on patient outcome.

Length of storage of red blood cells does not affect outcome in critically ill children

Sir: Length of red blood cell (RBC) storage has been proposed a contributing factor to adverse outcome after RBC transfusion. This may be explained by an impaired ability to transport or deliver oxygen, or the presence of leukocytes in stored RBC preparations producing potential deleterious pro-inflammatory mediators or bioactive lipids [1]. We hypothesized that length of RBC storage might explain our previously observed independent association between RBC transfusion and increased mortality, duration of mechanical ventilation (MV) and length of paediatric intensive care unit (PICU) stay in critically ill children [2]. For each time a patient was transfused in our previous study, length of RBC storage was retrieved from our hospital’s blood bank [2]. Since we observed a dose-outcome relation between the number of RBC transfusions and mortality, we separately looked at single transfusion and multiple transfusions. The effect of RBC transfusion on oxygenation was assessed by the oxygenation index (OI, mean airway pressure times FiO2 divided by PaO2) and PaO2/FiO2 ratio. RBC preparations were leukocyte-depleted, but not irradiated. Statistical analysis was performed using the Student t-test; linear regression analysis was applied to study correlations. P \ 0.05 was accepted as statistically significant. Data of 295 patients were studied, of whom 67 (22.7%) were transfused; 39 (58.2%) were transfused only once, the remaining 28 received multiple transfusions at different time intervals (range 2–14) (Table 1). Seventeen (5.8%) patients died. The mean length of RBC storage was 16.7 ± 0.6 days [25–75% interquartile range (IQR) 9–23 days]. Length of RBC storage was comparable between survivors and non-survivors. This remained after comparing single versus multiple transfusions. Differences in OI and PaO2/FiO2 ratio between the first day and fifth day after transfusion, duration of MV and length of PICU stay were not correlated with length of RBC storage. Our findings indicate that our previous reported observed independent association between transfusion of leucocyte-depleted RBC preparations and increased morbidity in critically ill children could not be explained by length of RBC storage. Mortality was also not influenced by length of RBC storage, although our study might not be powered to detect this. To our knowledge, although the issue of RBC transfusion has been extensively studied in critically ill adults, no other paediatric data on length of RBC storage and outcome in critically ill children have been reported. Results from retrospective and prospective

Dexamethasone reduces reintubation rate due to postextubation stridor in a high‐risk paediatric population

Objective: To study the effect of dexamethasone on postextubation stridor (PS) incidence and reintubation rate due to PS in a high-risk paediatric intensive care population. Patients and methods: All children aged between 4 wk and 6 y, who were intubated for at least 24 h and extubated between August 1999 and May 2002, were retrospectively included (n=60). Medical records of the included patients were studied; records of patients treated with dexamethasone prior to and following extubation (n=23) were compared with control patients who had not received prophylactic medication (n=37). Results: Nine patients in the control group developed significant postextubation stridor, necessitating nebulized epinephrine or glucocorticosteroids. In six of these children, reintubation as a result of postextubation stridor was indicated. None of the patients treated with dexamethasone developed severe postextubation stridor or required reintubation. Conclusions: The risk of postextubation stridor is relatively high in the group of children aged between 4 wk and 6 y with intubation exceeding 24 h. We found dexamethasone to be effective in preventing reintubation due to postextubation stridor in this paediatric high-risk group.

Spontaneous breathing during high-frequency oscillatory ventilation improves regional lung characteristics in experimental lung injury.

Background: Maintenance of spontaneous breathing is advocated in mechanical ventilation. This study evaluates the effect of spontaneous breathing on regional lung characteristics during high‐frequency oscillatory (HFO) ventilation in an animal model of mild lung injury.

Patient-Ventilator Asynchrony During Assisted Ventilation in Children.

Objective: To describe the frequency and type of patient-ventilator asynchrony in mechanically ventilated children by analyzing ventilator flow and pressure signals. Design: Prospective observational study. Setting: Tertiary PICU in a university hospital. Patients: Mechanically ventilated children between 0 and 18 years old and who were able to initiate and maintain spontaneous breathing were eligible for inclusion. Patients with congenital or acquired neuromuscular disorders, those with congenital or acquired central nervous system disorders, and those who were unable to initiate and maintain spontaneous breathing from any other cause were excluded. Interventions: None. Measurements and Main Results: All patients were ventilated in a time-cycled, pressure-limited mode with flow triggering set at 1.0 L/min by using the Evita XL (Dräger, Lubeck, Germany). Patient-ventilator asynchrony was identified by a random 30-minute continuous recording and an offline analysis of the flow and pressure signals. Patient-ventilator asynchrony was categorized and labeled into four different groups: 1) trigger asynchrony (i.e., insensitive trigger, double triggering, autotriggering, or trigger delay), 2) flow asynchrony, 3) termination asynchrony (i.e., delayed or premature termination), and 4) expiratory asynchrony. Flow and pressure signals were recorded in 45 patients for 30 minutes. A total number of 57,651 breaths were analyzed. Patient-ventilator asynchrony occurred in 19,175 breaths (33%), and it was seen in every patient. Ineffective triggering was the most predominant type of asynchrony (68%), followed by delayed termination (19%), double triggering (4%), and premature termination (3%). Patient-ventilator asynchrony significantly increased with lower levels of peak inspiratory pressure, positive end-expiratory pressure, and set frequency. Conclusions: Patient-ventilator asynchrony is extremely common in mechanically ventilated children, and the predominant cause is ineffective triggering.