Special considerations in paediatric intensive care

PAEDIATRICS e CRITICAL CARE

Special considerations in paediatric intensive care

Learning objectives After reading this article, you should be able to:

Norbert R Froese

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Abstract

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The modern-day paediatric intensive care unit (PICU) is staffed and equipped to provide care to the most critically ill children. It is by definition a low-volume, high-cost service. High staff-to-patient ratios are required both because of the potentially rapid evolution of critical illness in children and because of the complexity of the supportive therapy offered. Children are admitted to the PICU with a wide variety of medical illnesses and following diverse surgical procedures. Treatment strategies are complex. Recent international collaborative efforts have produced consensus treatment guidelines, which serve to promote the use of evidence-based, best practice therapies. This article reviews critical therapies and techniques which help define care in the PICU, and outlines the management of acute lung injury, traumatic brain injury and septic shock. Neonatal and cardiac intensive care medicine topics are outside the scope of this article.

airway management extremely difficult. Correct positioning of the endotracheal tube in the trachea is established on clinical criteria and confirmed by detection of exhaled CO2, blood gas analysis and radiographic imaging. Conventional mechanical ventilation in the PICU can be divided into control mode and support mode ventilation. In control mode ventilation, the work of breathing is borne entirely by the ventilator, whereas in support mode ventilation the patient’s own respiratory efforts are augmented. Combinations of these two modes are possible. Early in the course of therapy, control modes predominate, whereas support modes are increasingly used during the weaning stages. Volume control (VC) and pressure control (PC) are the basic forms of control mode ventilation. In both VC and PC ventilation, the frequency and duration of breaths are prescribed. In VC ventilation, the tidal volume is set. This tidal volume is delivered by means of a constant gas flow over the duration of the breath. In this form of ventilation, airway pressure increases over the course of each breath and peak airway pressure varies with changes in lung mechanics. In contrast, with PC ventilation, a fixed, prescribed airway pressure is maintained over the course of each breath, resulting in a diminishing flow pattern and variable tidal volumes. Advanced control modes such as pressure-regulated volume control (PRVC) are commonly used. In PRVC, tidal volumes are set, as with VC, but gas flow patterns are manipulated by the ventilator to approximate the constant inspiratory airway pressure of PC. Control modes that maintain constant inspiratory airway pressure, such as PC and PRVC, deliver higher tidal volumes for a given peak airway pressure, and thus are often preferred in cases in which high airway pressures are a concern. Pressure support ventilation (PSV) is the most common support mode of ventilation used in the PICU. In PSV, the timing and duration of each breath is determined by the patient, with each breath being supported, or augmented, by the application of a prescribed amount of additional airway pressure. Synchronized intermittent mandatory ventilation (SIMV) refers to control mode ventilation, during which the patient can take a spontaneous breath between mechanical breaths. In the PICU, control modes and support modes are often combined, with the application of PSV to the spontaneous breaths of SIMV. High-frequency oscillatory ventilation (HFOV) is a nonconventional ventilation mode in which a constant airway pressure is applied without interruption. Removal of carbon dioxide is achieved with very small tidal volumes, delivered at a high frequency (3e20 cycles per second). Because there is no

Keywords airway; brain; catheter; injury; intensive care; lung; paediatric; sepsis; support; ventilation

Approximately 40% of admissions to the paediatric intensive care unit (PICU) in the UK occur following cardiovascular and other surgical procedures.1 Over 80% of these surgical admissions are planned. Respiratory and cardiovascular illnesses constitute the greater part of the workload in the PICU (Figure 1).

Therapies and techniques in the PICU Airway management and mechanical ventilation The fundamentals of airway management in the PICU are similar to those of paediatric emergency airway control, where pulmonary aspiration is a significant risk. Pulmonary aspiration is a risk because many patients will not be fasted. In trauma cases, cervical spinal stabilization must be performed. Pharmacological agents are chosen with particular attention to the possibility of haemodynamic deterioration that can be caused by the administration of any sedative medication, and to the possibility of loss of airway with paralysis. Cuffed endotracheal tubes should be considered to ensure that an airway seal can be reliably achieved, thus avoiding the requirement for immediate or delayed endotracheal tube changes. This is particularly important in the case of facial burns, in which airway swelling can make delayed

Norbert R Froese MD FRCPC is a Consultant Anesthesiologist and Director of Cardiac Anesthesia at British Columbia’s Children’s Hospital, Vancouver, Canada. He obtained Royal College of Physicians of Canada certification in anaesthesia at the University of Manitoba, Winnipeg, and trained in paediatric anaesthesia, paediatric cardiac anaesthesia and paediatric critical care at the Children’s Hospital of Philadelphia. Conflicts of interest: none declared.

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list the critical therapies that define care in the paediatric intensive care unit describe the methods used to minimize risk in the use of paediatric central-line catheters list five therapeutic endpoints for the titration of fluid and inotropic medication in paediatric septic shock.

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Primary diagnostic group of admissions to UK paediatric intensive care units, for patients aged less than 16 years Unknown

342

Other

1980

Trauma

1639

Respiratory

11,007

Diagnostic group

Oncology

1598

Neurological

4924

Musculoskeletal

1630

Multisystem

132

Infection

2224

Gastrointestinal

2865

Endocrine/metabolic

1037

Cardiovascular

13,083

Body wall and cavities

977

Blood/lymphatic 0

403 2,000

4,000

6,000

8,000

10,000

12,000

14,000

Number of admissions From the Paediatric Intensive Care Audit Network. National Report of the Paediatric Intensive Care Audit Network January 2005–December 2007. Available at http://www.picanet.org.uk/, with permission

Figure 1

release of airway pressure during HFOV, lung recruitment, and thus oxygenation, is optimized for any given airway pressure. Non-invasive support mode ventilation, in which positive airway pressure is applied via a face mask, nasal mask or nasal cannulae, is increasingly being used in the PICU. Preferred modes of ventilation and ventilator settings vary with varying pulmonary disease patterns. Mechanical ventilation in the setting of acute lung injury (ALI) is discussed below. Central venous access Indications for placement of a central venous catheter (CVC) in the PICU include provision of secure venous access, delivery of vasoactive and inotropic drug infusions, administration of concentrated parenteral nutrition solutions and central venous pressure monitoring. Common sites for catheter placement include the internal jugular vein, the subclavian vein and the femoral vein. Multi-lumen catheters are frequently used and these are available in a variety of sizes for paediatric use. A 4 French 5 cm catheter can be used in the right internal jugular position in a typical full-term newborn. Catheter placement is performed by the catheter-over-wire Seldinger technique. Ultrasound guidance is replacing surface landmark techniques for the initial venous puncture and is associated with a decrease in insertion attempts and in inadvertent arterial puncture2 (Figure 2). Catheter-related bloodstream infection is a common complication that can be minimized by strict adherence to published prevention guidelines. Key components of published guidelines include maximal barrier precautions and 2% chlorhexidine skin preparation at the time of insertion, hand washing whenever the line is handled and prompt removal of unnecessary lines. In contrast to adult practice, there is no evidence in children to

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Portable ultrasound image obtained during right internal jugular cannulation of a 3.5 kg infant. The tip of a 22 guage intravenous catheter can clearly be located within the right internal jugular vein. a Transverse view; b longitudinal view. CA, carotid artery; RIJ, right internal jugular vein. Figure 2

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suggest that femoral vein CVC placement is associated with an increased infection rate. Central venous thrombosis at the site of cannulation is increasingly recognized. Diagnosis requires a high index of suspicion and confirmation with ultrasound Doppler imaging. Treatment involves prompt removal of the catheter and, in the absence of contraindications, can include thrombolysis and/or long-term anticoagulation with low-molecular-weight heparin or warfarin.

tolerated. Dialysis fluid is cyclically infused into the peritoneal cavity, allowed to dwell, drained and then re-infused via a peritoneal catheter. Peritoneal dialysis fluids typically contain physiological concentrations of sodium, chloride, magnesium, calcium and a base such as lactate, acetate or bicarbonate. Dialysis fluid is available with varying glucose concentrations between 1.5% and 4.25%, with the higher glucose concentration solutions promoting increased fluid removal owing to their increased osmolality. Typical peritoneal dialysis volumes are between 10 and 40 ml/kg/cycle, with larger volumes promoting increased fluid and solute exchange. Larger volumes are, however, associated with increased intra-abdominal pressure swings, which may cause cyclical decreases in blood pressure and impair ventilation. Continuous renal replacement therapies used in the PICU include slow continuous ultrafiltration (SCUF), continuous venovenous haemofiltration (CVVH) and continuous venovenous haemodialysis (CVVHD). With SCUF, blood is passed through a haemofilter, continuously removing water and small molecules. With CVVH, a larger ultrafiltrate volume is removed, and this is partially replaced with a balanced salt solution, resulting in net elimination of small molecules not included in the replacement solution. The relative volumes of ultrafiltration and replacement solution in CVVH are determined by the fluid balance goals of the therapy. CVVHD is similar to intermittent haemodialysis, in that solutes and water move between blood and dialysis fluid across an extracorporeal semipermeable membrane. Although less efficient than intermittent haemodialysis, full renal support can be achieved because therapy is uninterrupted. Continuous therapy results in slower changes in intravascular volume and serum osmolality and is thus better tolerated from a haemodynamic standpoint. A major limitation of all continuous renal replacement therapies is the requirement for large-bore central vascular access. A double-lumen central venous catheter is commonly placed to facilitate this. In the neonate, a 7 French catheter is required. Anticoagulation is required to prevent thrombus formation in the circuit. Systemic heparin is commonly used. In cases in which systemic anticoagulation is contraindicated, regional anticoagulation is used. This can be achieved by pre-filter administration of citrate to bind calcium, and post-filter administration of calcium to maintain normal systemic calcium levels. Similar administration of

Inotropic and vasoactive medications Continuous infusions of inotropic and vasoactive medications are used to provide haemodynamic support for patients in the PICU. The catecholamines exert their effect via stimulation of adrenergic receptors located in myocardial and peripheral vascular tissue. Stimulation of b1-adrenergic receptors increases heart rate and contractility, whereas stimulation of b2-receptors acts on the peripheral vasculature to cause vasodilation. a1Receptors are found on the peripheral vasculature and mediate vasoconstriction. Type III phosphodiesterase inhibitors inhibit the metabolism of cyclic adenosine monophosphate (cAMP). This causes peripheral vascular relaxation as well as increased myocardial contractility. Phosphodiesterase inhibitors enhance the reuptake of intracellular calcium, causing improved diastolic relaxation. Inotropic medications commonly used in the PICU are summarized in Table 1. Renal replacement therapy Support of a failing renal system is increasingly being recognized as a vital component of the overall critical care of the child with multiorgan system failure. Renal replacement therapies are effective in restoring fluid balance, normalizing serum solutes and electrolytes, normalizing acidebase balance and elimination of drugs and toxins. Fluid removal decreases interstitial oedema and improves lung and other organ function. Providing nutrition and other therapies requiring co-administration of fluid is facilitated by the reliable removal of the administered fluid volume. Peritoneal dialysis and continuous renal replacement therapy (CRRT) are the two modalities most often used in the PICU. Peritoneal dialysis relies on the exchange of fluids and electrolytes between the blood and dialysis fluid across the peritoneal membrane. It is relatively simple to implement, and is well

Commonly used inotropic medications in the paediatric intensive care unit Drug

Mechanism

Contractility

HR

SVR

PVR

Dose

Epinephrinea Dopaminea Dobutamine Milrinone

a,b stimulation a,b stimulation b > a stimulation Phosphodiesterase III inhibition

[ [ [ [

[ [ [ [

[ [ Y Y

[ [ Y Y

Norepinephrine

a > b stimulation

[

4

[

[

0.02e0.5 mg/kg/min 2e15 mg/kg/min 2e15 mg/kg/min Load 50 mg/kg 0.25e0.75 mg/kg/min 0.02e0.5 mg/kg/min

HR, heart rate; PVR, pulmonary vascular resistance; SVR, systemic vascular resistance. a

Alpha effects increase relative to beta effects (increased SVR, PVR) at higher dose range.

Table 1

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heparin and protamine sulphate before and after filtration is possible, but is used less often in paediatric practice. Continuous renal replacement therapy techniques can be associated with haemodynamic deterioration at the time of initiation. This is caused in part by activation of the inflammatory response as well as by binding of administered catecholamines to the fresh membrane. These effects can be minimized by a slow initiation protocol, and temporary doubling of catecholamine infusion rates.

ALI, including ARDS, mortality is reported to be between 18% and 27%. In children with ARDS, this figure is 29e50%.3 Mortality is lower in children than in adults. In addition to treating the underlying cause of ALI, children with ALI require supportive care to maintain oxygenation and to remove carbon dioxide during lung dysfunction. Although supplemental oxygen and mechanical ventilation are the primary means of providing respiratory support in ALI, both high levels of inspired oxygen (FiO2) and mechanical ventilation are themselves causes of lung injury. Mechanisms of ventilator-induced lung injury (VILI) include overdistension of aerated lung units from application of high airway pressures. Repeated opening and closing of atelectatic units also causes pulmonary injury. Modern ventilatory strategies in ALI are aimed at limiting FiO2 and minimizing VILI. In the absence of child-specific data, these strategies are based on adult recommendations. These include the use of small tidal volumes, not exceeding 6 ml/kg, and limiting peak inspiratory pressures to 30 cm H2O. It is important to apply sufficient positive airway pressure during expiration (PEEP). Determination of optimal PEEP is based either on FiO2 requirement or on static lung compliance data. Additional supportive therapies in paediatric ALI are discussed below. High-frequency oscillatory ventilation (HFOV) promotes the maintenance of open lung units by means of continuously applied airway pressure, while delivering only very small tidal volumes. This makes it attractive in the setting of ALI. HFOV is commonly used in paediatric ALI when the limits of conventional ventilation are being approached. However, although HFOV has been shown to improve oxygenation when compared with conventional ventilation, improvement in mortality or in days of ventilation has not been demonstrated. Placing the patient in the prone position improves oxygenation in ALI and allows for weaning of FiO2. In ALI, lung consolidation is non-heterogeneous, and is predominantly located in dependent dorsal lung units. Placing children in the prone position brings the more aerated lung units into a dependent position, where pulmonary blood flow is preferentially distributed. Similar to HFOV, neither improvement in mortality nor decrease in days of ventilation have been shown with prone positioning, despite the improvement in oxygenation. Selective pulmonary vasodilation also improves oxygenation by matching ventilation and perfusion in diseased lungs. Nitric oxide, a potent pulmonary vasodilator, is preferentially delivered to ventilated lung units as part of the inspiratory gas mixture. However, in clinical trials, initial improvements in oxygenation using nitric oxide therapy in ALI have not been sustained. The concept of pulmonary instillation of surfactant in children with ALI is attractive because of the secondary surfactant depletion in this condition, and because of the significant benefit of this therapy in premature neonates with primary surfactant deficiency. Clinical trial results, however, are non-conclusive, and surfactant therapy in ALI is not currently part of noninvestigative care in the PICU. Although ALI is an inflammatory condition, corticosteroid therapy does not have a role in ALI. In children with severe ARDS who cannot otherwise be supported, ECLS can be instituted to provide oxygenation and removal of carbon dioxide, and to allow for lung recovery. If

Extracorporeal life support Extracorporeal life support (ECLS) is a technique of mechanical replacement of heart and/or lung function that can be used to support children with severe cardiorespiratory failure. With ECLS, blood is drained from the body via a venous cannula, pumped through an oxygenator, where it is oxygenated and carbon dioxide is removed, and subsequently returned to the body. In cases requiring cardiac support, the oxygenated blood is returned to the arterial system, bypassing the heart and lungs; this is known as venoarterial (VA) ECLS. In cases of pulmonary dysfunction, oxygenated blood can be returned to the venous system, to be further pumped to the systemic circulation by the child’s heart; this is known as venovenous (VV) ECLS. Blood flow rates in ECLS equate to cardiac output, so large cannulae are required. In VA ECLS, the venous cannula is typically placed in the right atrium via the right internal jugular vein and the arterial cannula is placed at the junction of the innominate artery and the aorta via the right common carotid artery. Large-bore doublelumen venous cannulae are available for VV ECLS. Systemic anticoagulation with heparin is required to prevent blood clotting in the ECLS circuit. ECLS is associated with significant lifethreatening complications, which include massive surgical site haemorrhage, intracranial haemorrhage and infection. Although ECLS is a powerful support tool, its use is appropriate only in cases in which there is a reasonable expectation of recovery from the underlying organ dysfunction.

Acute lung injury Acute lung injury (ALI) is the term applied to inflammatory lung dysfunction that can result from a variety of precipitating causes. The pathophysiology of ALI includes inflammation-induced disruption of the alveolarecapillary membrane, flooding of the alveoli with oedema fluid, formation of hyaline membranes and surfactant depletion. Acute respiratory distress syndrome (ARDS) refers to severe ALI. The ‘A’ in ARDS originally referred to ‘adult’. This was changed to ‘acute’ in recognition that ARDS occurs in children as well. The definition of ALI and ARDS was agreed at the 1993 AmericaneEuropean consensus conference. ALI is now defined as disease with an arterial oxygen tension to FiO2 ratio (PaO2/FiO2) of less than 300, and ARDS as disease with a PaO2/FiO2 ratio of less than 200. The diagnosis of both ALI and ARDS requires bilateral pulmonary infiltrates on chest radiograph, and no evidence of left atrial hypertension. The incidence of ALI in ventilated children in the PICU has been reported to be 9%, with 80% of those going on to develop ARDS.3 Causes of ALI in children include direct pulmonary injury from viral or bacterial pneumonia, or from pulmonary aspiration, and indirect injury, for example from septic shock. In paediatric

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ECLS is used, it is important that it is initiated sufficiently early to avoid irreversible lung injury resulting from prolonged highpressure ventilatory support.

First-tier management of paediatric traumatic brain injury

Management of traumatic brain injury in children Traumatic brain injury (TBI) is a leading cause of death in childhood, and is responsible for significant morbidity in the paediatric population. Primary brain injury, which is incurred at the time of trauma, can realistically be addressed only by measures aimed at injury prevention. Secondary brain injury occurs in the hours to days after the primary insult. It results, in part, from cerebral ischaemia caused by brain swelling and increased intracranial pressure. Other causes of secondary brain injury include cerebral blood flow dysregulation, adverse effects of excitatory neurotransmitters, inflammation, oxidative stress and apoptosis.4 Paediatric intensive care is aimed at minimizing secondary brain injury. A comprehensive review of the literature in the management of TBI in children, with the participation of multiple international critical care, neurosurgery and trauma associations, was undertaken in 2002, and resulted in the publication of consensus guidelines in 2003. Although the strength of evidence for these guidelines is for the most part poor, they nonetheless represent a comprehensive consensus view of expert opinion, and have significantly influenced current practice in paediatric TBI. The consensus recommendations for first-line therapy are summarized in Figure 3. Early and aggressive implementation of therapies to reverse hypoxia and hypotension are of paramount importance in promoting optimal outcome in children with TBI. Interventions include ensuring a secure airway and optimal ventilation, with tracheal intubation if necessary, supplemental oxygen delivery, a careful evaluation of extracranial injuries and aggressive replacement of blood loss. Further therapy is aimed at controlling elevations in intracranial pressure (ICP) and optimizing cerebral perfusion pressure (CPP). Sustained elevations in ICP above 20 mm Hg are associated with worse outcome. CPP is a measure of perfusing blood pressure relative to ICP and is calculated by subtracting the ICP from mean arterial pressure. A CPP of 40e60 mm Hg is recommended. Blood pressure is managed by optimization of intravascular volume, as well as by administration of vasopressors such as norepinephrine if necessary. Placement of an ICP monitor to guide therapy is recommended and facilitates ICP- and CPP-directed therapy. Although several ICP monitoring strategies exist, placement of a ventriculostomy allows for therapeutic drainage of cerebrospinal fluid, in addition to ICP pressure monitoring. Simple measures to promote venous drainage of the head include keeping the head in the midline position and elevating the head of the bed by 30 . Adequate analgesia and sedation, prevention of hyperthermia with surface cooling and/or paracetamol, and administration of fosphenytoin or phenytoin (15e20 mg/kg loading dose and 2.5 mg/kg twice daily) to prevent seizure activity further controls ICP. Routine neuromuscular blockade is no longer recommended because seizure activity can be masked. Although hyperventilation will decrease ICP, this occurs by way of cerebral vasoconstriction, and thus at the expense of

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Surgery as indicated

GCS ≤ 8 Yes Insert ICP monitor Maintain CPP (age appropriate) Yes

No

↑ICP? Yes

Sedation and analgesia (HOB at 30°) Yes

No

↑ICP? Yes

Drain CSF if ventriculostomy present Consider repeating CT scan

Yes

No ↑ICP? Yes

Carefully withdraw ICP treatment

Neuromuscular blockade Yes

No

↑ICP? Yes

Mannitol PRN

Hyperosmolar therapy (3% saline infusion)

May repeat if serum osmolarity < 320

May continue if serum osmolarity < 360

Yes

↑ICP?

No

Yes Mild hyperventilation (PaCO2 30–35 mm Hg) Yes

No ↑ICP? Yes

Second-tier therapy CPP, cerebral perfusion pressure; CSF, cerebrospinal fluid; CT, computed tomography; GCS, Glasgow Coma Scale; HOB, head of bed; ICP, intracranial pressure; PRN, as needed. From Adelson PD, Bratton SL, Carney NA, et al. Guidelines for the acute medical management of severe traumatic brain injury in infants, children and adolescents. Chapter 17. Critical pathway for the treatment of established intracranial hypertension in pediatric traumatic brain injury. Pediatr Crit Care Med 2003; 4: S65–7, with permission.

Figure 3

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cerebral perfusion. Hyperventilation is not recommended therapy. Rather, current recommendations are to maintain the partial pressure of carbon dioxide (PCO2) in the normal or mildly decreased range. Administration of mannitol (0.25e0.5 g/kg/dose) or 3% hypertonic saline (0.1e1.0 ml/kg/h delivered on a sliding scale) moves water out of brain tissue by osmotic action and thus decreases intracranial volume. Both are recommended therapies to reduce ICP. Mannitol dosing can be repeated, providing serum osmolarity is less than 320 mOsm/l. Serum osmolarities as high as 360 mOsm/l are tolerated with hypertonic saline therapy. Some adult protocols limit hypertonic saline when serum sodium exceeds 155 mmol/l. Mannitol will induce an osmotic diuresis, and excess urinary volume loss must be replaced to avoid hypotension. Normothermia should be maintained in children with TBI. In a recently published multicentre trial, induced hypothermia to 32.5 C for 24 hours did not improve outcome in paediatric TBI.5 Relative risk of death was 1.4 in the hypothermia group, but this did not reach statistical significance.

accepted consensus guidelines for the critical care management of severe sepsis and septic shock, including recommendations for paediatric disease. These guidelines were updated and republished in 2008. Figure 4 outlines the recommended therapy for septic shock. In children, as in adults, early administration of appropriate antibiotics, within 1 hour of making the diagnosis of sepsis, is of paramount importance. Early establishment of vascular access, by the intraosseous route if necessary, followed by aggressive intravascular fluid augmentation is a vital early intervention in septic shock. Initial volume requirements are usually at least 40e60 ml/kg and are administered in 20 ml/kg increments. Often, significantly larger volumes are required. Initially, an isotonic crystalloid such as normal saline is the fluid of choice. No advantage of colloids over crystalloids has been shown. Although adult sepsis guidelines recommend transfusion of packed red cells in cases with decreased central venous oxygen saturation and a haematocrit of less than 30%, evidence to guide transfusion of red cells in children is lacking. Most children with septic shock will, in addition to intravascular volume administration, require inotropic support. Dopamine is the consensus recommendation for initial therapy. In patients with elevated systemic vascular resistance (SVR), as demonstrated by signs of decreased cardiac output but not hypotension, dobutamine is recommended. Shock resistant to these agents is treated with epinephrine or norepinephrine. Epinephrine is favoured for low cardiac output/high SVR states (‘cold shock’), whereas norepinephrine is preferred for shock states with normal-to-high cardiac output and low SVR (‘warm

Paediatric intensive care management of sepsis Sepsis is an important cause of injury and death in children, and is a major reason for admission to the PICU. The definition of severe sepsis in children is similar, but not identical, to the definition in adults and is summarized in Table 2. The mortality for severe sepsis in children is approximately 10%, which is, however, significantly less than that seen in adults. In 2004, a group of international experts in sepsis, representing 11 organizations, published the first internationally

Definitions of sepsis and septic shock from the 2002 Paediatric Consensus Conference Term

Definition

SIRS

The presence of at least two of the following criteria. One of the criteria in bold face must be included: Core temperature >38.5 or <36 C C Tachycardia in the absence of external stimulus, chronic drugs or painful stimuli, or bradycardia for children <1 year old C Tachypnoea or mechanical ventilation for an acute process not related to neuromuscular disease or anaesthesia C Leucocytosis or leucopenia or >10% immature neutrophils SIRS in the presence of, or as a result of, suspected or proven infection Sepsis plus one of the following: cardiovascular dysfunction OR acute respiratory distress syndrome, or two or more other organ dysfunctions Sepsis and cardiovascular dysfunction Despite administration of 40 ml/kg of fluid in 1 hour: C Hypotension OR C Need for vasoactive drug to maintain BP in normal range OR C Two of the following: C

Sepsis Severe sepsis Septic shock Cardiovascular dysfunction

C C C C C

Unexplained metabolic acidosis Increased arterial lactate Oliguria Capillary refill >5 seconds Core to peripheral temperature gap >3 C

BP, blood pressure; SIRS, systemic inflammatory response syndrome.

Table 2

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Approach to paediatric shock Recognize decreased mental status and perfusion Maintain airway and establish access according to PALS guidelines

0 min 5 min

Push 20 ml/kg isotonic saline or colloid boluses up and over 60 ml/kg Correct hypoglycaemia and hypocalcaemia Administer antibiotics Fluid refractory shock†

15 min Fluid responsive*

Establish central venous access, begin dopamine or dobutamine therapy and establish arterial monitoring

Observe in PICU

Fluid refractory-dopamine/dobutamine-resistant shock Titrate epinephrine for cold shock, warm epinephrine for warm shock to normal clinical endpoints and Scvo2 saturation ≥70% Catecholamine-resistant shock

60 min

Begin hydrocortisone if at risk for absolute adrenal insufficiency Normal blood pressure Cold shock ScvO2 saturation < 70%

Low blood pressure Cold shock ScvO2 saturation < 70%

Low blood pressure Warm shock ScvO2 saturation ≥70%

Add vasodilator or type III phosphodiesterase inhibitor with volume loading

Titrate volume and epinephrine

Titrate volume and norepinephrine

Persistent catecholamine-resistant shock Start cardiac output measurement and direct fluid, inotrope, vasopressor, vasodilator and hormonal therapies to attain CI > 3.3 and less than 6.0 l/min/m2

Refractory shock

Consider ECMO

*Normalization of blood pressure and tissue perfusion; †hypotension, abnormal capillary refill or extremity coolness. CI, cardiac index; ECMO, extracorporeal membrane oxygenation; PALS, paediatric advanced life support; PICU, paediatric intensive care unit; ScvO2, central venous oxygen saturation. From Dellinger RP, Levy MM, Carlet JM, et al. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2008. Crit Care Med 2008; 36: 296–327, with permission

Figure 4

shock’). In patients in whom further decreases in SVR are required, the phosphodiesterase inhibitor milrinone can be added to the therapy. Vasopressin has been used to increase SVR in cases of low SVR refractory to norepinephrine therapy, although there is no clear evidence for improved outcome. Haemodynamic therapy, including fluid and inotrope administration, is titrated to therapeutic endpoints. Recommended endpoints in paediatric septic shock include normalization of heart rate; a capillary refill time of less than 2 seconds; full volume pulses, both centrally and peripherally; warm extremities; urine output of more than 1 ml/kg/h; and a normal mental status. Achieving a central venous pressure of 8e12 mm Hg, a central venous saturation of 70% and normalization of serum lactate levels are endpoints recommended in adult sepsis and are applicable to paediatric patients. Normalization of blood pressure alone cannot be used as evidence for normalization of cardiac output. There is no good evidence to guide the clinician in the use of steroids in paediatric septic shock. Current recommendations are

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to limit stress dose steroid administration to only those patients with shock resistant to catecholamine therapy and who are at risk for adrenal insufficiency. This includes children with purpura, those treated chronically with steroids and those with pituitary or adrenal disease. In these children, hydrocortisone, 50 mg/m2/24 h, is recommended. Recent literature does not support previous recommendations for tight glucose control in critically ill adult patients.6 No recommendations are made in paediatric disease owing to lack of data. If an insulin infusion is initiated, then the adult recommendations of using a validated protocol to guide dose adjustments, of ensuring that a glucose calorie source is provided for the patient and of monitoring blood glucose values hourly until stable, and no less than 4 hourly for the duration of the infusion, are applicable to paediatric care as well. Activated protein C, which is recommended for severe sepsis in adults, has not been shown to be effective therapy when assessed in paediatric patients, and is associated with an increased incidence of haemorrhage; therefore, it is not recommended in children.

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4 Bishop NB. Traumatic brain injury: a primer for primary care physicians. Curr Probl Pediatr Adolesc Health Care 2006; 36: 318e31. 5 Hutchison JS, Ward RE, Lacroix J, et al. Hypothermia therapy after traumatic brain injury in children. N Engl J Med 2008; 358: 2447e56. 6 NICE-SUGAR Study Investigators, Finfer S, Chittock DR, Su SY, et al. Intensive versus conventional glucose control in critically ill patients. N Engl J Med 2009; 360: 1283e97.

Finally, ECLS has been successfully used to support children with severe septic shock, although its implementation is recommended only in those patients who cannot be supported with conventional therapy. A

REFERENCES 1 Paediatric Intensive Care Audit Network. National report of the Paediatric Intensive Care Audit Network January 2005eDecember 2007. Universities of Leeds and Leicester, 2008. Also available at: http://www.picanet.org.uk/Documents/General/Annual_Report_2008/ PICANet%20National%20Report%202005%20-%202007.pdf (accessed 22 March 2009). 2 Froehlich CD, Rigby MR, Rosenberg ES, et al. Ultrasound-guided central venous catheter placement decreases complications and decreases placement attempts compared with the landmark technique in patients in a pediatric intensive care unit. Crit Care Med 2009; 37: 1090e6. 3 Dahlem P, van Aalderen WM, Bos AP. Pediatric acute lung injury. Paediatr Respir Rev 2007; 8: 348e62.

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FURTHER READING Dellinger RP, Levy MM, Carlet JM, et al. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2008. Crit Care Med 2008; 36: 296e327. Department of Health. The acutely or critically sick or injured child in the district general hospital: a team response. Also available at: http:// www.dh.gov.uk/en/Publicationsandstatistics/Publications/ PublicationsPolicyAndGuidance/DH_062668 (accessed 24 May 2009). The Intercollegiate Committee for Training in Paediatric Intensive Care Medicine. Also available at: http://www.rcoa.ac.uk/index.asp? PageID ¼ 37 (accessed 24 May 2009).

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