Joan S. Roberts

Colloid volume expanders : Problems, pitfalls and possibilities

SummaryColloid solutions have been developed and used over the past 70 years as expanders of the intravascular space, based on an understanding of Starling’s law. Increasing osmotic pressure with colloidal products has remained an attractive theoretical premise for volume resuscitation. Indeed, colloids have been shown to increase osmotic pressure in clinical practice; however, the effects are shortlived. Lower molecular weight colloids exert a larger initial osmotic effect, but are rapidly cleared from the circulation. Larger molecules exert a smaller osmotic pressure that is sustained longer.The main drawback to colloid therapy lies in pathological states with endothelial injury and capillary leak, precisely the clinical scenario where colloids are commonly given. The colloid solution may leak into the interstitium and remain there exerting an osmotic gradient, pulling additional water into the interstitium.There are 4 general types of colloid products available for clinical use. Albumin is the predominant plasma protein and remains the standard against which other colloids are compared. Albumin, pooled from human donors, is in short supply and remains expensive. Dextrans have been used to prevent deep venous thrombosis and to lower blood viscosity during surgery. Hetastarch has been widely used as a plasma volume expander. It provides equivalent plasma volume expansion to albumin, but has been shown to alter clotting parameters in studies (prolonging the activated partial thromboplastin time and prothrombin time). Although severe coagulopathies have been reported in sporadic cases, hetastarch has not been shown to increase postoperative bleeding compared with albumin therapy, even in large doses (3 L/day).Despite some theoretical advantages compared with crystalloid therapy, colloid administration has not been shown to decrease the risk of acute lung injury or to improve survival. Specific indications for colloid products include hypoproteinaemic or malnourished states, patients who require plasma volume expansion who are unable to tolerate larger amounts of fluid, orthopaedic and reconstructive procedures requiring prevention of thrombus formation and leukapheresis.

Central nervous system complications during pediatric extracorporeal life support: incidence and risk factors.

Objective:Identify the incidence and risk factors for development of acute, severe central nervous system (CNS) complications of pediatric extracorporeal life support (ECLS). Design:Retrospective review of Extracorporeal Life Support Organization (ELSO) registry database. Setting:Pediatric intensive care units of 115 tertiary centers internationally. Patients:Pediatric patients, 1 month to 18 yrs of age, who had ECLS between the years 1981–2002. Measurements and Main Results:Data concerning 4,942 patients who underwent one run of ECLS were analyzed. Six hundred thirty-six patients (12.9%) developed acute, severe CNS complications. Patients who required ECLS during extracorporeal cardiopulmonary resuscitation (n = 161; 3.3%) were more likely to develop CNS complications (n = 42; 26.1%) than patients who did not have extracorporeal cardiopulmonary resuscitation (p < .001; odds ratio [OR], 2.48; 95% confidence interval [CI], 1.73–3.57). Stepwise logistic regression analysis of therapies patients received before initiation of ECLS showed that the use of a left ventricular assist device (p = .001; OR, 3.45; 95% CI, 1.64–7.22), bicarbonate (p < .001; OR, 1.61; 95% CI, 1.26–2.05), and vasopressor/inotropic medications (p = .035; OR, 1.22; 95% CI, 1.01–1.48) were significant independent predictors of development of CNS complications. Among patients who had pulmonary failure as an indication for ECLS, the CNS complication rate was significantly higher for those treated with venoarterial ECLS than those who had venovenous ECLS (13.5% vs. 5.7%; p < .001; OR, 0.43; 95% CI, 0.34–0.67). Multiple logistic regression analysis of the complications other than CNS complications associated with the use of ECLS showed that pH <7.20, creatinine concentration >3.0 mg/dL, use of inotropes, presence of myocardial stun, and requirement of cardiopulmonary resuscitation during ECLS independently predicted development of CNS complications. Conclusion:Patients who have metabolic acidosis, a bicarbonate or inotrope/vasopressor requirement, cardiopulmonary resuscitation, or a left ventricular assist device before initiation of ECLS are at greater risk for development of CNS complications. After initiation of ECLS, patients who develop renal failure or metabolic acidosis or undergo venoarterial ECLS should be closely monitored for development of CNS complications.

Cerebral hyperemia and impaired cerebral autoregulation associated with diabetic ketoacidosis in critically ill children

Objective:Cerebral edema associated with diabetic ketoacidosis is an uncommon but severe complication of insulin-dependent diabetes mellitus with unclear pathophysiology. We sought to determine whether cerebral edema in patients with diabetic ketoacidosis was related to changes in cerebral blood flow, autoregulation, regional cerebral saturation, or S100B. Design:Prospective case series. Setting:Pediatric intensive care unit of a tertiary children’s hospital. Patients:Six patients with diabetic ketoacidosis and altered mental status, requiring computed tomographic scan of the head. Interventions:Study evaluations included: 1) transcranial Doppler evaluations to determine middle cerebral artery flow velocities and cerebral autoregulation, defined by the autoregulatory index, at 6 and 36 hrs; 2) continuous monitoring of regional cerebral oxygenation on the left lateral forehead using near-infrared spectroscopy for the first 24 hrs of admission; 3) serial measurement of S100B as a marker of central nervous system injury; and 4) follow-up head computed tomographic scan. Results:Serial computed tomographic scans showed that four of six patients had changes in brain volume without overt cerebral edema. Initial scans showed narrowing of the third and lateral ventricles when compared with follow-up. There was no difference in middle cerebral artery flow velocities between admission and recovery at 36 hrs, despite Paco2 increasing during treatment. Cerebral flow was normal to increased, despite hypocapnia. Cerebral autoregulation was impaired in five of six patients at 6 hrs and normalized by 36 hrs. Mean regional cerebral oxygenation was measured in five of six patients and decreased linearly with time. Two patients showed maximal regional cerebral oxygenation before returning to baseline. There were no periods of low regional cerebral oxygenation in any patient at any time. No elevation in S100B was found. Conclusions:We found normal to increased cerebral blood flow, elevated regional cerebral oxygenation, impaired autoregulation, and changes in brain volume in clinically ill pediatric patients with diabetic ketoacidosis. We found no evidence of cerebral ischemia. These findings suggest that the pathophysiology of cerebral edema in diabetic ketoacidosis may involve a transient loss of cerebral autoregulation, allowing a paradoxic increase in cerebral blood flow and the development of vasogenic cerebral edema.

Change in blood– brain barrier permeability during pediatric diabetic ketoacidosis treatment

Objective: Cerebral edema is a devastating complication of pediatric diabetic ketoacidosis. We aimed to examine blood–brain barrier permeability during treatment of diabetic ketoacidosis in children. Design: Prospective observational study. Setting: Seattle Children’s Hospital, Seattle, WA. Patients: Children admitted with diabetic ketoacidosis (pH <7.3, HCO3 <15 mEq/L, glucose >300 mg/dL, and ketosis). Interventions: None. Measurements and Main Results: Subjects underwent two serial paired contrast-enhanced perfusion (gadolinium) and diffusion magnetic resonance imaging scans. Change in whole brain and regional blood–brain barrier permeability (permeability ratio*100 and % permeability ratio change) between illness and recovery were determined. Time 0 reflects start of insulin treatment. Thirteen children (median age 10.0 ± 1.1 yrs; seven female) with diabetic ketoacidosis were enrolled. Permeability ratio increased from time 1 (first magnetic resonance image after time 0) to time 2 (second magnetic resonance image after time 0) in the frontal cortex (ten of 13 subjects), occipital cortex (ten of 13 subjects), and basal ganglia (nine of 13). Whole brain permeability ratio increased from time 1 to time 2 (160%) and regional increase in permeability ratio was greatest in the frontal cortex (148%) compared with the occipital cortex (128%) and basal ganglia (112%). Conclusions: Overall, whole brain and regional blood–brain barrier permeability increased in most subjects during diabetic ketoacidosis treatment. The frontal region had more blood–brain barrier permeability than other brain regions examined.

Massive ibuprofen overdose requiring extracorporeal membrane oxygenation for cardiovascular support

Objective: Ibuprofen is rarely associated with severe toxicity. We report a massive ibuprofen overdose that resulted in refractory hypotension requiring extracorporeal membrane oxygenation (ECMO) for cardiovascular support. Design: Individual case report. Setting: Pediatric intensive care unit of a tertiary care hospital. Patient: A 14-yr-old male presented with apnea and cardiovascular collapse after a nonaccidental ingestion of approximately 50 g of ibuprofen. His laboratory evaluation demonstrated an anion gap metabolic acidosis and elevated lactate levels. Interventions: The patient required pressor support with norepinephrine, phenylephrine, and vasopressin infusions. Due to refractory hypotension, he was placed on ECMO. His serum ibuprofen level at an estimated 5–10 hrs postingestion was 776 &mgr;g/mL (therapeutic 20–30 &mgr;g/mL). Urine toxicological screen for drugs of abuse, serum acetaminophen, salicylate, and carboxyhemoglobin levels showed that these levels were not elevated. The patient developed high-output renal failure, pulmonary hemorrhage, and gastric bleeding, all of which resolved by hospital day 3. Measurements and Main Results: ECMO was discontinued on hospital day 4, inotropic support was discontinued, and the patient was extubated on hospital day 5. He was transferred to an inpatient psychiatric unit on hospital day 9 with no identifiable medical sequelae. Conclusions: Although ibuprofen overdose typically has few consequences, severe hypotension, renal failure, and gastrointestinal bleeding can occur. We report the first known case of successful ECMO therapy for ibuprofen overdose.

Acute severe asthma: Outcome and Medicaid insurance.

Objective Economically disadvantaged children receive less preventive asthma care and more inpatient care. Studies have not evaluated the association of insurance status on children with severe exacerbations. We evaluated differences in severity of illness, resource use, and outcome associated with Medicaid insurance among children receiving intensive care for asthma. Design Retrospective cohort study. Setting Fourteen American pediatric intensive care units participating in the Pediatric Intensive Care Evaluations database. Methods Patients with a primary diagnosis of asthma treated from May 1995 to February 2000 were identified. Demographic information and clinical data were evaluated to determine whether there was an association between Medicaid insurance, severity of illness, and length of stay. Results Twenty-six percent of the children had Medicaid insurance; 22% of children with Medicaid insurance received mechanical ventilation compared with 15% of those with commercial insurance and 16% in a health maintenance organization. After adjustment for severity of illness (Pediatric Risk of Mortality III and use of invasive therapies), Medicaid insurance was significantly associated with increased length of stay in the intensive care unit and hospital. Among children who received mechanical ventilation, patients with Medicaid also received ventilator support significantly longer. Conclusions Asthmatic children receiving Medicaid had longer pediatric intensive care unit and hospital stays and an increased risk of mechanical ventilation compared with asthmatic children with commercial or health maintenance organization insurance. Further studies are needed to evaluate differences in outcome and resource utilization for economically disadvantaged asthmatic children.

Cerebral oxygenation in neonatal and pediatric patients during veno-arterial extracorporeal life support.

Objective: To observe the effects of right carotid artery ligation and variations in extracorporeal life support (ECLS) flow on regional cerebral oxygenation index (rSO2i) measured using near infrared spectroscopy. Design: Prospective observational study. Setting: Tertiary childrens hospital. Patients: Eleven neonatal and pediatric patients requiring veno-arterial ECLS support between June 2000 and March 2003. Interventions: Near infrared spectroscopy probe placement on left and right frontal regions of patients undergoing ECLS, before vessel cannulation or within 24 hrs of initiation of ECLS. Measurements and Main Results: Regional cerebral oxygenation was measured every minute for 72 hrs or until the patient was decannulated. The effect of cannulation on rSO2i from each hemisphere of the brain and the relationship between ECLS flow and rSO2i during ECLS support and “trialing off” periods were determined. Ligation of the right carotid artery resulted in a 12–25% decrease in rSO2i from baseline in the right frontal region for a duration ranging from 17 to 45 mins before returning toward baseline. No substantial change in the left frontal region rSO2i was detected during cannulation. Following this depression in rSO2i on the right, there was a transient increase above baseline in rSO2i observed in both hemispheres on initiating ECLS. No correlation between ECLS flow and rSO2i was found over the 72-hr period. Periods of “trialing off” ECLS were not related to any change in rSO2i in either hemisphere. Conclusions: This study demonstrated no relationship between ECLS flow and rSO2i changes during the 72-hr observation period. A brief period of cerebral oxygen desaturation of the right frontal region at the time of right carotid ligation was seen in all three study patients examined during cannulation, followed by an increased rSO2i with initiation of ECLS flow. Near infrared spectroscopy measurement may offer an important adjunct for neurologic monitoring of ECLS patients.

The influence of inhaled nitric oxide on cerebral blood flow and metabolism in a child with traumatic brain injury

IMPLICATIONS The effects of inhaled nitric oxide (INO) on cerebrovascular hemodynamics are not well established. We report no adverse cerebral effects with INO therapy in a child with traumatic brain injury.

Hypertension Despite Dehydration During Severe Pediatric Diabetic Ketoacidosis

Deeter KH, Roberts JS, Bradford H, Richards T, Shaw D, Marro K, Chiu H, Pihoker C, Lynn A, Vavilala MS. Hypertension despite dehydration during severe pediatric diabetic ketoacidosis.

Outcome of Pediatric Hematopoietic Stem Cell Transplant Recipients Requiring Mechanical Ventilation

Purpose: To assess the risk factors for intensive care unit admission among children receiving hematopoietic stem cell transplantation (HSCT) and to test the hypothesis that multiple organ failure (MOF) increases the odds of death among HSCT patients who receive mechanical ventilation (MV). Methods: The chart of all consecutive HSCTs at Seattle Children’s Hospital and pediatric HSCT patients admitted to the pediatric critical care unit of a tertiary care pediatric hospital from January 2000 to September 2006 were reviewed retrospectively. Results: Charts of 266 HSCT patients were reviewed. Nonmalignant disease compared to hematologic malignancy, acute graft versus host disease grades III and IV, and second transplant increased the odds of pediatric intensive care unit admission. Among patients receiving MV for >24 hours, 9 (25%) survived for 6 months, while 8 patients (22%) were long-term survivors with a median follow-up time of 3.6 years, a significant improvement compared to a long-term survival of 7% (odds ratio 0.25, 95% confidence intervals: 0.09-0.72, P = .01) reported in a previously published cohort of pediatric HSCT patients at the same institution from 1983 to 1996. Cardiovascular failure, duration of MV for greater than 1 week, and prolonged receipt of continuous renal replacement therapy (CRRT) increased the risk of mortality. Conclusions: Six-month survival of pediatric HSCT patients was 25% and the odds of death were increased by cardiovascular failure but not by MOF. Receipt of mechanical support (ventilation, CRRT) or cardiovascular support (inotropic agents) decreased the likelihood of long-term survival.