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The collapsed newborn in the emergency department

Open ArchivePublished:June 27, 2018DOI:https://doi.org/10.1016/j.bjae.2018.05.004
      By reading this article, you should be able to:
      • List and describe the common causes of neonatal collapse.
      • Describe investigations which play a key role in making a diagnosis.
      • Demonstrate how to manage the common causes of neonatal collapse in the acute phase.
      • The most common causes of neonatal collapse are congenital heart disease, sepsis, and metabolic diseases.
      • It is important to attempt to make a diagnosis and commence resuscitation simultaneously.
      • If duct-dependent congenital heart disease is considered the diagnosis, immediate prostaglandin infusion is advised with target oxygen saturations between 75% and 85%.
      • Congenital adrenal hyperplasia can present as shock with a salt loss crisis, which requires treatment with i.v. saline, hydrocortisone, and correction of electrolyte abnormalities.
      • A high index of suspicion for non-accidental injury requires a low threshold for referral to child protection professionals.
      As anaesthetists, it is not uncommon to encounter a newborn who has had a sudden unexpected postnatal collapse (SUPC) in the emergency room. This is a crisis situation where resuscitation and diagnosis need to be performed simultaneously by a multidisciplinary team. This article focusses on the various pathologies that can present as SUPC.
      The incidence of SUPC varies between 2.6 and 133 cases per 100 000. This includes severe apparent life-threatening events and sudden unexpected death in infancy.
      • Herlenius E.
      • Kuhn P.
      Sudden unexpected postnatal collapsed of newborn infants: a review of cases, definitions, risks and preventative measures.
      In this context, the ‘postnatal’ period is defined as the first 7 days after birth of apparently healthy, term babies (normal Apgar score at 5 min and deemed to be healthy enough to receive normal newborn care).
      • Clare Becher Julie
      British Association of Perinatal Medicine
      Guidelines for the investigation of newborn infants who suffer a sudden and unexpected postnatal collapse in the first week of life.

      Main differential diagnoses

      The most common causes of SUPC are congenital heart disease (CHD), sepsis, and metabolic disorders (Table 1).
      • Herlenius E.
      • Kuhn P.
      Sudden unexpected postnatal collapsed of newborn infants: a review of cases, definitions, risks and preventative measures.
      There should also always be a high index of suspicion for non-accidental injury (NAI).
      Table 1Differential diagnoses of SUPC

      Paediatric emergencies. Collapsed neonate. Available from: http://www.paediatricemergencies.com/index.php/2016/01/09/collapsed-neonate/ [Accessed 14 June 2017]

      • Reuter S.
      • Moser C.
      • Baack M.
      Respiratory distress in the newborn.
      Diagnostic categoryExample
      Congenital heart diseaseObstructive left heart lesions: hypoplastic left heart syndrome, coarctation of the aorta, interrupted aortic arch, critical aortic stenosis

      Obstructive right heart lesions: tetralogy of Fallot, critical pulmonary stenosis, tricuspid/pulmonary atresia

      Transposition of the great vessels

      Single ventricle circulation

      Neonatal cardiomyopathy

      Fetal arrhythmia

      Cardiac tamponade

      Large atrial or ventricular septal defect
      Sepsis/infectionCommon bacteria: maternal group B streptococcus, Listeria monocytogenes, Escherichia coli, Staphylococcus aureus

      Common viruses: Herpes simplex virus, enteroviruses, parechoviruses

      Common fungal: candida spp.
      Metabolic/endocrine disordersCAH

      Maternal thyrotoxicosis

      Congenital hypothyroidism

      Hypoglycaemia (multiple different inborn errors of metabolism, e.g. hyperinsulinism, fatty acid oxidation defects)

      Urea cycle defect

      Organic acidaemias

      Glycogen storage disorders

      Mitochondrial disorders
      NAIAbusive head injury

      Hypoglycaemia secondary to neglect

      Hypovolaemia: long bone fracture, intra-abdominal injury, intracranial haemorrhage

      Hypothermia
      RespiratoryPulmonary hypertension

      Neonatal pneumonia

      Pneumothorax

      Large congenital pulmonary airway malformation

      Manifest shortly after birth: meconium aspiration syndrome, transient tachypnoea of the newborn, respiratory distress syndrome
      Gastro-intestinalIntussusception (rare)

      Malrotation/volvulus

      Necrotising enterocolitis

      Hirschsprung enterocolitis
      NeurologicalSeizures

      Congenital malformations (e.g. anencephaly, lissencephaly, hydrocephalus)
      ToxinsOpioids

      Diphenhydramine

      Small dose killers (e.g. beta antagonist, calcium channel antagonist, digoxin, sulfonylureas)
      The incidence of CHD that is dependent on a patent ductus arteriosus is 6–8 per 1000 live births. It is suspected as a diagnosis if the patient presents with cyanosis, hypoxia despite oxygen therapy, and tachypnoea without lung pathology. Pulmonary oedema may be seen in late presentations. A pathological murmur, absent femoral pulses, hepatomegaly, cardiomegaly, or lactic acidosis unresponsive to initial resuscitation is supportive of a diagnosis of CHD.
      • Yun S.W.
      Congenital heart disease in the newborn requiring early intervention.
      Early onset sepsis occurs in the first week of life with an incidence in the UK of 0.5 per 1000 live births. Mortality is 10% and there is a risk of severe, permanent disability. Signs of sepsis are non-specific and may occur with other inflammatory and metabolic conditions.
      • Du Pont-Thibodeau G.
      • Joyal J.S.
      • Lacroix J.
      Management of neonatal sepsis in term newborns.
      Age-specific criteria have been devised that help point the practitioner towards a diagnosis of sepsis in the neonatal period. The following criteria are for babies aged between 0 and 1 week:
      • Goldstein B.
      • Giroir B.
      • Randolph A.
      International Consensus Conference on Pediatric Sepsis
      International pediatric sepsis consensus conference: definitions for sepsis and organ dysfunction in pediatrics.
      • (i)
        Temperature >38.5°C or <36°C;
      • (ii)
        HR >180 or <100 beats min−1;
      • (iii)
        Ventilatory frequency >50 bpm;
      • (iv)
        Leucocyte count >34×109 cells L−1.
      In paediatric patients with shock, the presence of hypotension is a late finding and is therefore not included in the criteria above. However, if present, it indicates impending cardiorespiratory failure. Risk factors for neonatal sepsis include preterm birth, very low birth weight, chorioamnionitis, and premature rupture of membranes more than 24 h before delivery.

      Paediatric emergencies. Collapsed neonate. Available from: http://www.paediatricemergencies.com/index.php/2016/01/09/collapsed-neonate/ [Accessed 14 June 2017]

      Metabolic disorders present in a variety of ways so early diagnosis is difficult. The child may present with energy insufficiency, evidenced by hypoglycaemia and lactic acidosis in conditions such as hyperinsulinism, glycogen storage disease, and mitochondrial disorders. The patient may present with intoxication from accumulation of a particular substance (e.g. galactose in galactosaemia, or ammonia in urea cycle defects).
      • Mohamed S.
      Recognition and diagnostic approach to acute metabolic disorders in the neonatal period.
      Metabolic diseases are more common in infants with consanguineous biological parents, so a relevant family history should be obtained. The diagnosis should be considered in patients with metabolic acidosis, lactic acidosis, hyperammonaemia, or hypoglycaemia.

      Paediatric emergencies. Collapsed neonate. Available from: http://www.paediatricemergencies.com/index.php/2016/01/09/collapsed-neonate/ [Accessed 14 June 2017]

      Ambiguous genitalia, failure to thrive, and electrolyte abnormalities can also indicate metabolic disorders.
      • Padidela R.
      • Hindmarsh P.C.
      Mineralocorticoid deficiency and treatment in congenital adrenal hyperplasia.
      Congenital adrenal hyperplasia (CAH), one of the more common metabolic disorders, can present in the first week of life with a salt loss crisis, which can be fatal. CAH is considered as a diagnosis if there is lethargy, vomiting, ambiguous genitalia (in a female baby), and decreased consciousness.
      It is everyone's responsibility to think of NAI as an underlying cause or factor in a case of SUPC. NAI is the leading cause of both childhood traumatic injury and death in the USA. Intracranial haemorrhage may present with seizures, a bulging fontanelle, and decreased consciousness.

      Paediatric emergencies. Collapsed neonate. Available from: http://www.paediatricemergencies.com/index.php/2016/01/09/collapsed-neonate/ [Accessed 14 June 2017]

      Abusive head injury, previously known as ‘shaken baby’ syndrome, occurs as a result of disruption of bridging veins, and is a clinical triad of intracranial haemorrhage (most commonly subdural haematoma), retinal haemorrhage, and encephalopathy. A careful history and a high index of suspicion are essential in identifying these infants.
      • Paul A.R.
      • Adamo M.A.
      Non-accidental trauma in paediatric patients: a review of epidemiology, pathophysiology, diagnosis and treatment.
      Detailed management of NAI is beyond the scope of this article.

      Initial management

      Initial assessment and management must be rapid, stepwise, and multidisciplinary.

       Airway

      Newborns with SUPC often require airway intervention. Indications include neuroprotection for patients with intracranial haemorrhage or cerebral oedema, loss of airway reflexes because of a depressed consciousness level, or impending respiratory arrest. In addition, high-dose prostaglandin infusions may lead to apnoeic periods, in which case ventilation may be required.
      All members of the team should be prepared with allocated roles and a clear awareness of the risks of tracheal intubation. The increased incidence of difficult airway in the newborn should be anticipated.
      • Schmidt J.
      Incidence of difficult airway in 19 500 children aged 0 to 17 years.
      During induction of anaesthesia, bradycardia may occur suddenly, so atropine 20 μg kg−1 should either be prepared or given before intubation.
      The patient's lungs are usually pre-oxygenated with 100% oxygen. However, if a diagnosis of a patent ductus arteriosus (PDA)-dependent lesion is considered, administration of lower concentrations of oxygen (30–40%) may be used, as higher concentrations may result in excessive blood flow through the lungs, known as pulmonary overcirculation, which itself leads to increased pulmonary vascular resistance. Generally, a Miller or Robertshaw size 1 laryngoscope blade is recommended for a term newborn. Appropriate tracheal tube sizes and depths of insertion are shown in Table 2.
      • Kemply S.T.
      • Moreiras J.W.
      • Petrone F.L.
      Endotracheal tube length for neonatal intubation.

      Dagle J. Technique for insertion of an endo-tracheal tube. University of Iowa Stead Family Children's Hospital. Available from: https://uichildrens.org/health-library/technique-insertion-endotracheal-et-tube [Accessed 17 March 2017]

      Table 2Sizes and insertion depths of tracheal tubes
      • Kemply S.T.
      • Moreiras J.W.
      • Petrone F.L.
      Endotracheal tube length for neonatal intubation.

      Dagle J. Technique for insertion of an endo-tracheal tube. University of Iowa Stead Family Children's Hospital. Available from: https://uichildrens.org/health-library/technique-insertion-endotracheal-et-tube [Accessed 17 March 2017]

      Gestational age (weeks)Weight (g)Insertion depth (cm)Tube size—internal diameter (mm)
      23–24500–6005.52.5 if

      <1000 g or <28 weeks
      25–26700–8006.0
      27–29900–10006.53.0 if

      1000–2000 g or 28–34 weeks
      30–321100–14007.0
      33–341500–18007.53.5 if

      >2000 g or >34 weeks
      35–371900–24008.0
      38–402500–31008.5
      41–433200–42009.03.5–4.0
      Usually, anaesthesia is induced using a classic or modified rapid-sequence technique, although there is essentially little or no evidence to support that this is the best method of induction. There is a high incidence of cardiovascular instability on induction of anaesthesia, making resuscitation beforehand vital. Preinduction resuscitation involves administration of i.v. fluid boluses and consideration of starting an infusion of inotropic drugs. It is also worthwhile preparing adrenaline 1 μg kg−1 as a bolus dose in case of haemodynamic instability after administering i.v. anaesthetic agents. Medications used can include varying combinations of ketamine, fentanyl, and neuromuscular blockers, amongst others. Response to i.v. anaesthetics may take longer than expected as there may be a prolonged circulation time. As newborns have high oxygen consumption and a closing capacity that exceeds the function residual capacity, rapid oxygen desaturation is likely. Consideration should therefore be given to gentle artificial ventilation of the lungs after induction of anaesthesia.

      Paediatric emergencies. Collapsed neonate. Available from: http://www.paediatricemergencies.com/index.php/2016/01/09/collapsed-neonate/ [Accessed 14 June 2017]

       Breathing

      Target oxygen saturations depend on the presumed underlying pathology. In conditions such as sepsis or raised ICP, oxygen saturations >95% are desirable. In most types of PDA-dependent CHD, an appropriate target for pre-ductal saturations (measured on the right hand) and post-ductal saturations (measured on either foot) is 75–85%.

      Paediatric emergencies. Collapsed neonate. Available from: http://www.paediatricemergencies.com/index.php/2016/01/09/collapsed-neonate/ [Accessed 14 June 2017]

      The reason to measure oxygen saturation both before and after the PDA orifice in the aorta is that post-ductal saturations are lower than pre-ductal saturations because of mixing of pulmonary blood through the patent ductus arteriosus. In addition, a nasogastric tube may be required in the event of gastric insufflation during bag-mask ventilation.

       Circulation

      I.V. access should be secured as rapidly as possible, with prompt progression to attempting intra-osseous access if difficulty is encountered. In a patient aged <1 week, the umbilical vein may be patent and is an option for venous access regardless of post-conceptional age. Ultrasound-guided line insertion is preferred for central venous access. If transposition of the great vessels is suspected, femoral access should be avoided, as percutaneous balloon atrial septostomy is typically accessed through the femoral vein. Some practitioners avoid internal jugular vein cannulation if a single ventricle circulation is suspected, as the patient might eventually need a Fontan procedure.

      Paediatric emergencies. Collapsed neonate. Available from: http://www.paediatricemergencies.com/index.php/2016/01/09/collapsed-neonate/ [Accessed 14 June 2017]

      A desirable MAP for a term neonate is 40 mm Hg. In a premature neonate, a MAP in mm Hg synonymous to the corrected gestational age is generally considered acceptable, though debate continues in the literature. As previously stated, BP (arterial or venous) is a poor measure and a late and unreliable sign of haemodynamic compromise; more attention should be paid to signs of end-organ perfusion, such as capillary refill time, urine output, tone, responsiveness, and peripheral pulses.
      Crystalloid boluses should be administered in 10 ml kg−1 aliquots, followed by reassessment of the patient after each bolus. If the patient has required more than 40 ml kg−1 of fluid and is responding poorly, an adrenaline infusion may be commenced at 0.1–1 μg kg−1 min−1.

      Paediatric emergencies. Collapsed neonate. Available from: http://www.paediatricemergencies.com/index.php/2016/01/09/collapsed-neonate/ [Accessed 14 June 2017]

      Haemoglobin should be maintained, especially in anaemic patients or if there is a history of blood loss. Blood transfusion may be necessary. A haemoglobin concentration <10 g d−1 until 7 days of age, or <7.5 g dl−1 after 8 days of age should be maintained, by blood transfusion if necessary.

      Joint United Kingdom blood transfusion and tissue transplantation services professional advisory committee. Neonatal transfusion. Available from: http://www.transfusionguidelines.org/transfusion-handbook/10-effective-transfusion-in-paediatric-practice/10-2-neonatal-transfusion [Accessed 17 March 2017]

      If shock remains unresponsive to fluids and inotropes, hydrocortisone 2.5 mg kg−1 may be administered every 6 h.

      Paediatric emergencies. Collapsed neonate. Available from: http://www.paediatricemergencies.com/index.php/2016/01/09/collapsed-neonate/ [Accessed 14 June 2017]

       Additional management

      It is important to administer i.v. broad-spectrum antibiotics with or without aciclovir within an hour to all newborns with SUPC, ideally after taking blood cultures. However, obtaining a sample should not delay the administration of antibiotics. It is also essential to keep the patient warm, manage seizures, and correct electrolyte abnormalities and hypoglycaemia.

      Paediatric emergencies. Collapsed neonate. Available from: http://www.paediatricemergencies.com/index.php/2016/01/09/collapsed-neonate/ [Accessed 14 June 2017]

      The importance of good communication with parents cannot be overemphasised. Often, there are feelings of guilt and anxiety that can be eased somewhat by consistent and clear information. This can involve updates on what is happening and why, with time given for questions. Parents may also find it helpful to be given written information and knowing the results of investigations.
      • Clare Becher Julie
      British Association of Perinatal Medicine
      Guidelines for the investigation of newborn infants who suffer a sudden and unexpected postnatal collapse in the first week of life.

      Specific management

       CHD

      Diagnostic echocardiography is readily available in most centres. It is a useful and rapid investigation which can determine the likelihood of CHD in a neonate with SUPC and should be considered at the earliest opportunity.
      There are two important principles of treatment in a patient with CHD. Firstly, a patent ductus arteriosus must be maintained to provide systemic perfusion. Prostaglandin infusions are used to achieve this. Possible adverse effects of prostaglandin infusions include apnoeic periods, hyperthermia, and hypotension. The adverse effects increase in incidence as the dose of the infusion increases. A low dose infusion can be started at 5 ng kg−1 min−1 if it is thought that the ductus arteriosus is still patent. However, in a newborn presenting with SUPC, it is more likely that the ductus arteriosus has closed, in which case a high infusion rate should be started, from 20 ng kg−1 min−1 to a maximum of 100 ng kg−1 min−1.

      Paediatric emergencies. Collapsed neonate. Available from: http://www.paediatricemergencies.com/index.php/2016/01/09/collapsed-neonate/ [Accessed 14 June 2017]

      Secondly, flow must be balanced between the systemic and pulmonary circulations, avoiding a larger proportion of the cardiac output going to the pulmonary circulation.
      The balance of flow is important in lesions with parallel pulmonary and systemic circulations, because an increase in pulmonary blood flow leads to a decrease in systemic blood flow, compromising myocardial perfusion, and resulting in tissue hypoxia. This phenomenon of an unbalanced circulation manifests clinically as excessively high systemic arterial saturations, but oliguria, cool peripheries, metabolic acidosis, and myocardial dysfunction also occur. Pulmonary overcirculation can result in the neonate appearing very pink, but becoming profoundly shocked. An example of an unbalanced circulation occurring is the administration of a high inspired oxygen to a patient with hypoplastic left heart syndrome. Aiming to increase pulmonary vascular resistance will maintain balance between the pulmonary and systemic circulations.
      • Dice J.E.
      • Bhatia J.
      Patent ductus arteriosus: an overview.
      A balanced circulation is maintained by increasing pulmonary vascular resistance or decreasing systemic vascular resistance. This may include adjusting ventilator settings to avoid a high inspired oxygen, aiming for a PaCO2 of 5–6 kPa, a systemic arterial saturation of 80%, and by applying a modest PEEP (4–6 cm H2O).
      • Yun S.W.
      Congenital heart disease in the newborn requiring early intervention.

       Sepsis

      In cases of suspected sepsis, resuscitation within the first 6 h of recognition is essential. This may include fluid boluses and inotropic support, with noradrenaline most commonly being first-line, and addition of adrenaline, dobutamine, or both in patients with cardiac dysfunction. Once shock is resolved, there may be a need for continuous veno-venous haemofiltration in cases of refractory fluid overload.
      • Du Pont-Thibodeau G.
      • Joyal J.S.
      • Lacroix J.
      Management of neonatal sepsis in term newborns.
      A lumbar puncture can be deferred in a sick neonate during active resuscitation. If the possibility of sepsis is deemed to be low and results of initial microbial testing are negative after 2 days, antibiotics should be stopped, as prolonged antibiotic therapy (more than 5 days) is associated with necrotising enterocolitis, increased incidence of late-onset sepsis, and increased mortality.
      • Du Pont-Thibodeau G.
      • Joyal J.S.
      • Lacroix J.
      Management of neonatal sepsis in term newborns.
      • Polin R.A.
      Management of neonates with suspected or proven early-onset bacterial sepsis.

       Metabolic disorders

      In all neonates with SUPC, important immediate investigations include arterial blood gases, serum lactate, glucose, and ammonia concentrations.
      • Mohamed S.
      Recognition and diagnostic approach to acute metabolic disorders in the neonatal period.
      These investigations are particularly useful if considering a metabolic cause. If these results are normal, other causes of SUPC can be considered in the acute phase. If abnormal, patients should be managed so that normal physiology and values are restored. A diagnostic test for a specific metabolic condition can take days or weeks to be returned. An expert in paediatric metabolic medicine should be consulted in the interim.
      CAH is one of the more commonly encountered metabolic causes of SUPC. CAH is a result of insufficient mineralocorticoid and corticosteroid production, which are responsible for maintaining salt/water balance and circulating volume. CAH is also associated with electrolyte abnormalities such as hypoglycaemia, hyponatraemia, and hyperkalaemia. In addition, the condition can involve poor cardiac function with a decreased responsiveness to catecholamines, resulting in shock. Management includes concurrent treatments of hypovolaemia and electrolyte abnormalities. Fluid boluses of saline 20 ml kg−1 are administered with reassessment after each bolus. Hypoglycaemia should be corrected using dextrose. Early administration of hydrocortisone will aid in the correction of electrolyte abnormalities. Hyperkalaemia should be aggressively treated, with the addition of calcium gluconate to ensure cardioprotection. Further management will have close involvement of paediatric endocrinologists.
      • Padidela R.
      • Hindmarsh P.C.
      Mineralocorticoid deficiency and treatment in congenital adrenal hyperplasia.

      Wilson TA, Rosenbloom AL. Congenital adrenal hyperplasia treatment and management. Medscape. Available from: http://emedicine.medscape.com/article/919218-treatment [Accessed 27 March 2017]

      Hyperammonaemia (ammonia >150 μmol L−1 in a neonate), particularly when associated with respiratory alkalosis, suggests a urea cycle defect. In the presence of a metabolic acidosis, the hyperammonaemia is more likely to be secondary and suggestive of an organic acid disorder. Hyperammonaemia can present with lethargy, poor feeding, tachypnoea, hepatomegaly, seizures, and coma. The presentation can also mimic sepsis.
      • Levy H.
      • Picker J.
      Neonate/infant/child with hyperammonaemia. New England consortium of metabolic programs.
      In all babies with SUPC, ammonia levels should be measured urgently.

      Paediatric emergencies. Collapsed neonate. Available from: http://www.paediatricemergencies.com/index.php/2016/01/09/collapsed-neonate/ [Accessed 14 June 2017]

      Treatment within the first 24 h is necessary to limit neurological damage, which could be irreversible the longer it is left untreated. Treatment involves stopping all protein intake and administering fluids with dextrose and Intralipid®, aiming for a calorie intake of 120–130 kcal kg−1 day−1. The use of an ammonia scavenger medication such as sodium benzoate or arginine will be necessary. Haemodialysis should be considered, particularly if the ammonia concentration is markedly increased (e.g. >300 μmol L−1), as this is the most effective way to eliminate ammonia from the body.
      • Levy H.
      • Picker J.
      Neonate/infant/child with hyperammonaemia. New England consortium of metabolic programs.
      Neonatal hypoglycaemia can result in permanent neurological damage if not treated promptly, including developmental delay and recurrent seizures. Symptoms and signs of hypoglycaemia include decreased tone and alertness, convulsions, sweating, and arrhythmias. Neonatal hypoglycaemia is not defined by a single value; post-conceptional age, weight, and the clinical condition must be taken into consideration. Generally speaking, a blood glucose concentration <2.0 mmol L−1 in a term infant within the first 72 h of life could warrant treatment. Repeated levels of <2.6 mmol L−1 may also require correction. An initial bolus of 10% dextrose 2–3 ml kg−1 is given. A continuous infusion of dextrose may also be necessary, with blood glucose retested 30 min after starting the infusion. If higher amounts of dextrose are required, these may be administered in a higher concentration via a central line to avoid irritation to the peripheral vascular system and fluid overload.

      Summary

      The management of SUPC is highly challenging, given the wide variety of differential diagnoses that can present in this manner. Patients often have highly unstable physiology and require the team to carry out rapid resuscitation whilst simultaneously attempting to make a diagnosis. Close involvement of the relevant paediatric subspecialties is required for further management.

      Declaration of interest

      There is no declaration of interest to be declared.

      MCQs

      The associated MCQs (to support CME/CPD activity) will be accessible at www.bjaed.org/cme/home by subscribers to BJA Education.

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      Biography

      Niharika Lal DTMH, Dip HIV Man (SA) is a specialty trainee in the West of Scotland who has also worked in London, South Africa, and Zambia.
      Terry Varshney MDCM, FRCP is a paediatric emergency physician at the Children's Hospital of Eastern Ontario. Her major clinical and research interests are education through simulation and point of care ultrasound.