Andy Petros

Cerebro-splanchnic oxygenation ratio (CSOR) using near infrared spectroscopy may be able to predict splanchnic ischaemia in neonates

Abstract. Objective: To investigate whether near infrared spectroscopy (NIRS) can detect differences in oxyhaemoglobin signal when applied to the abdomens of neonates with surgically proven splanchnic ischaemia. Design: Prospective, observational cohort study. Setting: Tertiary neonatal referral centre. Patients: Medical and surgical neonates were studied. Two groups were identified, neonates with acute abdomens referred for surgery and those with normal abdomens admitted for medical reasons. Interventions: Tissue oxygenation indexes (TOI) of cerebral and splanchnic regions were measured using near infrared spectroscopy (NIRS) and their relative values expressed as a cerebro-splanchnic oxygenation ratio (CSOR). Measurements were made on admission or immediately prior to surgery and subsequently repeated on a daily basis, whenever possible, until discharge from our unit. The area under the receiver operating characteristic (ROC) curve was evaluated and optimum diagnostic cut-off values determined. Results: Forty neonates were studied: 10 with acute abdomens, including four with necrotising enterocolitis (NEC), 29 controls with normal abdomens and one with cerebral hypoxic ischaemic injury. Median CSOR for the control group was 0.96 (interquartile range 0.83–1.02) whereas the acute abdomen group had a significantly lower median CSOR value of 0.66 (0.45–0.69) (p<0.001). The area under the ROC was 0.91 (95% confidence limits 0.78–1.00) for CSOR. Taking a boundary value of CSOR for the prediction of splanchnic ischaemia as less than 0.75, intestinal ischaemia was identified with a positive predictive value of 0.75 (0.43–0.95) and excluded with a negative predictive value of 0.96 (0.81–1.0). This was a better performance than using abdominal TOI alone. Conclusions: By comparing the TOI of cerebral and splanchnic regions it may be possible to establish the presence of normal splanchnic perfusion and detect when splanchnic ischaemia develops. CSOR had a 90% (56–100%) sensitivity to detect splanchnic ischaemia in neonates. Further work is necessary to confirm these early findings and establish whether abdominal NIRS has a clinical role in detecting splanchnic ischaemia.

Comparison of the bispectral index monitor with the Comfort score in assessing level of sedation of critically ill children.

ObjectiveTo compare the value of bispectral index as a monitor of sedation in critically ill children with a validated sedation scoring system.DesignProspective convenience sample.SettingPaediatric intensive care unit in a tertiary paediatric centre.Patients and participantsForty-three critically ill children receiving sedation and mechanical ventilation.Measurements and resultsSimultaneous recording of bispectral index (BIS) and assessment of depth of sedation using the Comfort score were performed at regular intervals. To determine if BIS could detect episodes of arousal, times of endotracheal suctioning and the corresponding BIS score were recorded. There was an overall moderate correlation between BIS scores and Comfort scores (r=0.50, r2=0.25, p<0.0001). Children who had a neurological reason for their current admission (n=25) showed a weaker correlation (r=0.26, r2=0.06, p<0.007) than those (n=15) with normal neurology (r=0.51, r2=0.26, p<0.0001). There were no significant differences in the rise in BIS following endotracheal suctioning among any of the predefined depths of sedation. There was a correlation of r=0.84 (r2=0.71) (SE of slope 0.49, CI95 1.79–3.88) for mean BIS values for each individual Comfort score from 8–23. Using Spearmans rank correlation of Comfort versus mean BIS, the correlation coefficient was r=0.92.ConclusionsBispectral index scores correlate with Comfort scores to a moderate degree. BIS is able to discriminate between light and deep levels of sedation, but not between deep and very deep levels of sedation. The BIS monitor may provide a useful method for assessing sedation in critically ill children, especially those receiving neuromuscular blockers.

Comparison of hyperventilation and inhaled nitric oxide for pulmonary hypertension after repair of congenital heart disease

BackgroundPulmonary hypertension is associated with congenital heart lesions with increased pulmonary blood flow. Acute increases in pulmonary vascular resistance (PVR) occur in the postoperative period after repair of these defects. These increases in PVR can be ablated by inducing an alkalosis with hyperventilation (HV) or bicarbonate therapy. Studies have shown that these patients also respond to inhaled nitric oxide (iNO), but uncertainty exists over the relative merits and undesirable effects of HV and iNO. HypothesisAlkalosis and iNO are equally effective in reducing PVR and pulmonary artery pressure (PAP) in children with pulmonary hypertension after open heart surgery. SettingCritical care unit of a tertiary care pediatric hospital. DesignProspective, randomized, crossover design. PatientsTwelve children with a mean PAP > 25 mm Hg at normal pH after biventricular repair of congenital heart disease. InterventionsPatients were assigned to receive iNO or HV (pH > 7.5) in random order, and the effect on hemodynamics was measured. Each treatment was administered for 30 mins with a 30-min washout period between treatments. Finally, both treatments were administered together to look for a possible additive effect. Measurements and Main ResultsCardiac output and derived hemodynamic parameters using the dye dilution technique. Hyperventilation, achieved by an increase in ventilator rate without a change in mean airway pressure, decreased Paco2 from a mean (sd) of 43.7 ± 5.3 to 32.3 ± 5.4 mm Hg and increased pH from 7.40 ± 0.04 to 7.50 ± 0.03. This significantly altered both pulmonary and systemic hemodynamics with a reduction in PAP, PVR, central venous pressure, and cardiac output and an increase in systemic vascular resistance. In comparison, iNO selectively reduced PAP and PVR only. The reduction in PVR was comparable between treatments, although addition of iNO to HV resulted in a small additional reduction in PVR. An additional decrease in PAP was seen when HV was added to iNO, attributable to a reduction in cardiac output rather than a further decrease in PVR. ConclusionsInhaled NO and HV are both effective at lowering PAP and PVR in children with pulmonary hypertension after repair of congenital heart disease. The selective action of iNO on the pulmonary circulation offers advantages over HV because a decrease in cardiac output and an increase in SVR are undesirable in the postoperative period.

Characteristics of deaths occurring in hospitalised children: changing trends

Background: Despite a gradual shift in the focus of medical care among terminally ill patients to a palliative model, studies suggest that many children with life-limiting chronic illnesses continue to die in hospital after prolonged periods of inpatient admission and mechanical ventilation. Objectives: To (1) examine the characteristics and location of death among hospitalised children, (2) investigate yearwise trends in these characteristics and (3) test the hypothesis that professional ethical guidance from the UK Royal College of Paediatrics and Child Health (1997) would lead to significant changes in the characteristics of death among hospitalised children. Methods: Routine administrative data from one large tertiary-level UK children’s hospital was examined over a 7-year period (1997–2004) for children aged 0–18 years. Demographic details, location of deaths, source of admission (within hospital vs external), length of stay and final diagnoses (International Classification of Diseases-10 codes) were studied. Statistical significance was tested by the Kruskal–Wallis analysis of ranks and median test (non-parametric variables), χ2 test (proportions) and Cochran–Armitage test (linear trends). Results: Of the 1127 deaths occurring in hospital over the 7-year period, the majority (57.7%) were among infants. The main diagnoses at death included congenital malformations (22.2%), perinatal diseases (18.1%), cardiovascular disorders (14.9%) and neoplasms (12.4%). Most deaths occurred in an intensive care unit (ICU) environment (85.7%), with a significant increase over the years (80.1% in 1997 to 90.6% in 2004). There was a clear increase in the proportion of admissions from in-hospital among the ICU cohort (14.8% in 1998 to 24.8% in 2004). Infants with congenital malformations and perinatal conditions were more likely to die in an ICU (OR 2.42, 95% CI 1.65 to 3.55), and older children with malignancy outside the ICU (OR 6.5, 95% CI 4.4 to 9.6). Children stayed for a median of 13 days (interquartile range 4.0–23.25 days) on a hospital ward before being admitted to an ICU where they died. Conclusions: A greater proportion of hospitalised children are dying in an ICU environment. Our experience indicates that professional ethical guidance by itself may be inadequate in reversing the trends observed in this study.

Human albumin administration in critically ill patients. Evidence needs to be shown in paediatrics.

Editor—We are concerned that the Cochrane Injuries Group’s meta-analysis regarding administration of albumin1 may alter the practice of resuscitating hypovolaemic hypotensive children, infants, and neonates. Although we are affiliated to the Institute of Child Health, we want to emphasise that this article does not reflect our own clinical practice, and at present we believe that it provides no compelling evidence to change our practice. We reviewed the 32 articles in the three groups. We identified only one paediatric study (So et al) in the hypovolaemia group, in which 63 preterm infants received albumin for hypotension. In the burns group there is only one paediatric study (n=70), in which albumin was given to maintain arbitrary serum concentrations (Greenhalgh et al). Finally, in the hypoproteinaemic group there are two studies of 64 neonates that addressed several hypotheses, including whether albumin was detrimental to respiratory status (Greenough et al) and was beneficial in weight gain (Kanarek et al). In a third study (n=27) that assessed the use of bicarbonate in acidotic neonates only the control groups of 5% dextrose and albumin were compared (Bland et al). We are now faced with concerns from parents about the “killer fluid,” and our junior staff are confused about the appropriate fluid to use for resuscitation of critically ill children. Have we been put into a legally indefensible position by this report from the Cochrane Injuries Group? We continue to use albumin for several reasons. To produce the same sustained increase in blood pressure as a 20 ml/kg bolus of albumin, up to five times as much volume of crystalloid would have to be given based on their relative oncotic pressures.2 This increased volume of crystalloid may lead to problems with fluid overload, hyperchloraemia in renal dysfunction, and pulmonary oedema. One leading manufacturer supplies £11.5 million of albumin to British hospitals each year.3 We must be certain that stopping the use of albumin is not a financially driven decision. We would be prepared to accept that albumin may be detrimental on the basis of appropriate data. At present we do not think, however, that there is enough evidence for us to stop using albumin for resuscitation in this population. In an attempt to resolve this controversy in a responsible manner we are about to embark on a prospective study to assess the safety of albumin use in children. Would the authors of the meta-analysis be prepared to enrol patients into such a study or would they consider it unethical?

Terlipressin bolus induces systemic vasoconstriction in septic shock.

Objective To report the use of a synthetic, long-acting, vasopressin analog, terlipressin, as an effective vasoconstrictor in septic shock. Design Case report. Setting A 22-bed pediatric intensive care unit in a tertiary referral center. Patient An 11-yr-old male with multiple-organism Gram-negative septic shock with high normal cardiac output as assessed by pulse contour analysis and low systemic vascular resistance despite norepinephrine infusion. Intervention Two peripherally administered doses of terlipressin (0.5 mg). Measurements and Main Results Each dose of terlipressin was associated with a rapid increase in systemic vascular resistance, despite weaning and discontinuation of norepinephrine infusion from 0.15 &mgr;g·kg−1·min−1 lasting approximately 6 hrs. Conclusion Terlipressin may be useful for sepsis-induced vasodilation.

Angiotensin for septic shock unresponsive to noradrenaline

Two children with severe septic shock are reported. One had meningococcal septicaemia and the other Escherichia coli septicaemia. They remained hypotensive despite high concentrations of conventional inotropes and vasopressors. In one child, using a pulmonary artery catheter, extended haemodynamic variables were measured. To restore blood pressure, in both cases, an infusion of angiotensin II was used; there was significant improvement in clinical status, resulting in a rapid reduction in the concentration of inotropes required. Both patients successfully survived their septic episodes. Angiotensin II in cases of severe refractory septic hypotension in the paediatric population offers an extra therapeutic manoeuvre.

Near infrared spectroscopy can detect changes in splanchnic oxygen delivery in neonates during apnoeic episodes.

Sir: The pathogenesis of necrotising enterocolitis (NEC) is still unknown. Proposed risk factors include prematurity, the presence of bacteria within the lumen of the gut [3], and enteral feeding [2]. We hypothesised that alteration in the splanchnic oxygen delivery may be the ®nal common pathway which links these diverse risk factors. Near infrared spectroscopy (NIRS) can determine changes in concentration of oxyhaemoglobin (HbO2), deoxyhaemoglobin (Hb) and regional blood volume (Hbvol) and has an established role in continuous, non-invasive, in-vivo monitoring of cerebral oxygenation [1]. This study was approved by the local research ethics committee. Simultaneous measurements were made of peripheral oxygen saturation (SpO2), heart rate, abdominal HbO2, Hb and Hbvol. Infrared light was emitted and received from small optodes (Niro 500, Hamamatsu Photonics, Japan) placed 23 mm apart upon the abdomen just above the umbilicus and protected from light. We report three neonates with apnoea. Case 1, an infant of 28 weeks gestation weighing 0.975 kg required ileal resection for intestinal perforation. Four days after tracheal extubation, at 2 weeks of age, she developed frequent episodes of apnoea and bradycardia having up to 20 self-limiting desaturations per day. The lowest SpO2 was 65%. She subsequently developed extensive NEC and died. Case 2, an infant of 33 weeks gestation, weighing 3.3 kg, was referred at 8 weeks of age because of up to 10 apnoeic episodes per day. Investigation revealed gastro-oesophageal re ̄ux and aspiration, necessitating surgical treatment. Case 3, an infant of 37 weeks gestation, weighing 1.8 kg, was monitored during weaning from mechanical ventilation. Two attempts to wean supplemental oxygen to room air failed. After settling he was given his routine feed while still being monitored. In all three cases, a fall in SpO2 coincided with a fall in gastrointestinal HbO2 signal and rise in gastro-intestinal Hb. Although episodes of systemic desaturation recovered within 2 min, recovery of HbO2 and Hb was delayed and took an extra 3 min. Such rapid changes in gastro-intestinal oxygen delivery observed with NIRS have not been previously reported. Case 3 also demonstrates that after an enteral feed both the gastro-intestinal blood volume and oxygen delivery increased. Repeated episodes of apnoea and hypoxia causing systemic desaturation may result in chronic ischaemia of the gut due to delayed re-oxygenation even though there is rapid recovery in SpO2. Thus, although hypoxia is considered to be a minor risk factor in NEC, signi®cant splanchnic hypoxia apparently occurs during periods of desaturation and lasts longer than has until now been appreciated.

Fulminant pertussis: a multi-center study with new insights into the clinico-pathological mechanisms.

Pertussis carries a high risk of mortality in very young infants. The mechanism of refractory cardio‐respiratory failure is complex and not clearly delineated. We aimed to examine the clinico‐pathological features and suggest how they may be related to outcome, by multi‐center review of clinical records and post‐mortem findings of 10 patients with fulminant pertussis (FP). All cases were less than 8 weeks of age, and required ventilation for worsening respiratory symptoms and inotropic support for severe hemodynamic compromise. All died or underwent extra corporeal membrane oxygenation (ECMO) within 1 week. All had increased leukocyte counts (from 54 to 132 × 109/L) with prominent neutrophilia in 9/10. The post‐mortem demonstrated necrotizing bronchitis and bronchiolitis with extensive areas of necrosis of the alveolar epithelium. Hyaline membranes were present in those cases with viral co‐infection. Pulmonary blood vessels were filled with leukocytes without well‐organized thrombi. Immunodepletion of the thymus, spleen, and lymph nodes was a common feature. Other organisms were isolated as follows; 2/10 cases Para influenza type 3, 2/10 Moraxella catarrhalis, 1/10 each with respiratory syncytial virus (RSV), a coliform organism, methicillin‐resistant Staphylococcus aureus (MRSA), Haemophilus influenzae, Stenotrophomonas maltophilia, methicillin‐sensitive Staphylococcus aureus (MSSA), and candida tropicalis. We postulate that severe hypoxemia and intractable cardiac failure may be due to the effects of pertussis toxin, necrotizing bronchiolitis, extensive damage to the alveolar epithelium, tenacious airway secretions, and possibly leukostasis with activation of the immunological cascade, all contributing to increased pulmonary vascular resistance. Cellular apoptosis appeared to underlay much of these changes. The secondary immuno‐compromise may facilitate co‐infection. Pediatr Pulmonol. 2009; 44:970–980. ©2009 Wiley‐Liss, Inc.

Should religious beliefs be allowed to stonewall a secular approach to withdrawing and withholding treatment in children

Religion is an important element of end-of-life care on the paediatric intensive care unit with religious belief providing support for many families and for some staff. However, religious claims used by families to challenge cessation of aggressive therapies considered futile and burdensome by a wide range of medical and lay people can cause considerable problems and be very difficult to resolve. While it is vital to support families in such difficult times, we are increasingly concerned that deeply held belief in religion can lead to children being potentially subjected to burdensome care in expectation of ‘miraculous’ intervention. We reviewed cases involving end-of-life decisions over a 3-year period. In 186 of 203 cases in which withdrawal or limitation of invasive therapy was recommended, agreement was achieved. However, in the 17 remaining cases extended discussions with medical teams and local support mechanisms did not lead to resolution. Of these cases, 11 (65%) involved explicit religious claims that intensive care should not be stopped due to expectation of divine intervention and complete cure together with conviction that overly pessimistic medical predictions were wrong. The distribution of the religions included Protestant, Muslim, Jewish and Roman Catholic groups. Five of the 11 cases were resolved after meeting religious community leaders; one child had intensive care withdrawn following a High Court order, and in the remaining five, all Christian, no resolution was possible due to expressed expectations that a ‘miracle’ would happen.