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Sedation for children undergoing cardiac catheterization: a review of literature.

Byline: Syed Muhammad Abbas, Abdul Rashid and Hammad Latif

Abstract

Management of children with congenital heart disease has been a great challenge for anaesthesiologists especially during cardiac catheterization. General anaesthesia with positive pressure ventilation can alter the intra-cardiac pressures as well as shunt fraction. Therefore deep sedation with pain free and spontaneously breathing patient on room air is preferred by the cardiac interventionist. A wide variety of drug regimens have been used for both general anaesthesia and monitored anaesthesia care. We reviewed the most common drugs used during the last 50 years for this procedure. The advent of new drugs has given better control on the level and duration of sedation with decreased untoward effects. A complete understanding of pathophysiology of the disease as well as the effects of intervention in a particular individual can provide a safe anaesthetic management.

Keywords: Congenital heart disease, Cardiac catheterization, Sedation, Anaesthesia.

Introduction

The history of catheterization dates back to 1844, when Claude Bernard1 inserted a mercury thermometer into the carotid artery of a horse and advanced it through the aortic valve into the left ventricle to measure blood temperature.

Later in 1929, a German surgical trainee, Werner Forssmann,2 inserted a urological catheter in his own forearm and guided it into his right atrium. In return, he was fired from his position at the hospital but later won the Nobel Prize in 1956.

The use of cardiac catheterization and angiography as a diagnostic tool was first described in man by Cournand3 and in children with congenital heart disease by Bing et al4 in 1947. Interventional catheterization was first performed in 1953 by Rubio-Alvarez5 to treat pulmonary stenosis. In 1966 the balloon atrial septostomy was developed by Rashkind and Miller6 which was the first paediatric and the first intra cardiac transcatheter procedure.

Cardiac catheterization in children with congenital heart disease can be performed under general anaesthesia, but monitored anaesthesia care (MAC) with spontaneously breathing patient on room air is the preferred method by the cardiologist.

Preoperative Assessment:

The preoperative evaluation of children with congenital heart disease undergoing cardiac catheterization, is a challenging task because of the wide range of anatomic and physiologic abnormalities. A thorough understanding of the anomalies enables the anaesthetist to choose a suitable technique for a particular patient.

A detailed history includes the gestational age, feeding reluctance, playing activities, cyanotic spells, continuous cough, failure to gain weight and bronchospasm. Physical examination should include the airway abnormalities, measurement of SpO2, blood pressure, and assessment of pulses in all extremities and difficulty for vascular access. Compromised heart may show signs of failure i.e. tachycardia with low volume pulse, a gallop rhythm, tachypnoea, difficulty in feeding, excessive perspiration, jugular venous distention, pulmonary congestion or hepatomegaly. Presence of increased respiratory rate, diaphoresis, intercostals muscles retraction, nasal flaring, and use of accessory respiratory muscles indicate poor respiratory reserve.

Nearly 28% of patients show associated anomalies or syndromes which include musculoskeletal abnormality (8.8%), neurological defects (6.9%), and genitourinary irregularities (5.3%) but the most common is the Down's syndrome (9%). Atlanto - occipital subluxation is common in Down's syndrome which can lead to quadriplegia during laryngoscopy and tracheal intubation. Pharmacologic therapy usually includes diuretics and drugs for afterload reduction. Prostaglandin E1 (PGE1) infusion to maintain the patency of ductus arteriosus may be present. Need for supplemental oxygen or respiratory support may be necessary if pulmonary congestion or pulmonary oedema is severe.

The plans for pre medication,

Table-1: Common procedures in catheterization laboratory.

A. Diagnostic catheterization

B. Interventional catheterization

Pulmonary artery angioplasty

Aortic coarctation angioplasty

Patent ductus arteriosus (PDA) occlusion or stenting

Ventricular septal defect closure

Atrial septal defect dilation

Atrial septal defect closure

Balloon atrial septostomy

Aortic valve dilation

Pulmonary valve dilation

Mitral valve dilation

Pericardiocentesis

Stent in pulmonary vein.

Table-2: Common drugs for premedication.

Drugs###Doses mg/kg

Ketamine###PO 2-10 IV .25-1.0 - IM 1-4.0

Chloral Hydrate###PO: 25-100

Promethazine###PO 0.1-1.0

Midazolam###PO 0.25-0.75 - Intranasal 0.1-0.3

Diazepam###PO 0.1-0.4

PO: Per OS. IM: Intramuscular.

(Table-2) provision of deep sedation along with the possibility of general anaesthesia, with tracheal intubation, blood transfusion, and postoperative care including the possibility of ventilatory support should be discussed with the family.

If the patient has a permanent pacemaker in place, the indications for pacing, underlying rhythm, device type and its functional status must be reviewed.

Appropriate laboratory studies include complete blood count (CBC), blood urea nitrogen (BUN), creatinine, electrolytes, coagulation studies, a screen for antibodies, and a cross match for appropriate blood products. Diuretic therapy may result in dehydration, hypochloremic metabolic alkalosis, or hypokalaemia.

The chest radiograph and transthoracic Echo report gives a valuable information regarding the cardiac anatomical abnormalities as well as pressure in different chambers of heart and great vessels.

American society of anesthesiologist (ASA) fasting guidelines, should be followed as in any case for general anaesthesia.

Unlike adults, paediatric group need moderate to deep sedation

Table-3: Ramsay Score.

Score###Description

0###Awake, oriented

1###Agitated, anxious

2###Awake, co-operative

3###Sleeping, but co-operative

4###Deep sedation, quick reaction to pain stimuli

5###Deep sedation, slow reaction to pain stimuli

6###Deep sedation, no reaction to pain stimuli.

Table-4: Commonly use Opioids for Sedation.

Drug###IV Bolus Dose###Infusion

Morphine###0.1-0.2 mg/kg###10-40 ug/kg/h

Fentanyl###1-3 ug/kg###1-10 ug/kg/h

Remifentanil###1 ug/kg###0.5-6 ug/kg/h

Alfentanil###15-25 ug/kg###0.4-2ug/kg/min

(Table-4, Ramsay Score) to keep them immobile during the procedure. Although there is no ideal deep sedation technique which is widely accepted but the advent of new short acting drugs have given better control on sedation. Since acidosis hyperoxaemia, hypoxia and positive pressure ventilation all exert significant disturbance in the haemodynamic calculations, a spontaneously breathing patient on room air, stable haemodynamics and normal blood gases are required with an appropriate immobility.

Monitoring:

Standard monitoring should be used as defined by ASA guidelines. Baseline ECG, SpO2, noninvasive blood pressure should be taken before starting sedation. Respiratory monitoring can be performed via lateral flow CO2 measurement tube placed closed to the mouth or in the oropharynx. Serial arterial blood gas should be checked once arterial line is established by the cardiologist.

Clinical scores like Ramsay score is the most common tool for monitoring the levels of sedation. However, during last one decade ectroencephalographic findings, such as the bispectral index (BIS), auditory evoked potentials have become popular methods for objective assessement of the level of consciousness.

DPT Mixture:

The combination of Meperidine(M), Promethazine(P), and Chlorpromazine(C) (MPC, Cardiac Cocktail) has been widely used for more than 40 years for paediatric sedation in a variety of cases. It comprises of Meperidine 25 mg/ml, Promethazine 6.5 mg/ml, and chlorpromazine 6.5 mg/ml which was used in a dose of 0.1 ml/kg.7 In 1958 Smith8 used this mixture intramuscularly in 670 patients. He found it a very promising method as only one patient had depressed breathing, only 5-10 mm Hg fall in MAP and a few mm Hg increase in PAP. One death was reported directly related to the mixture of drugs due to the use of full dose in a very sick child.

In 1969 Goldberg et al9 found an increase in pulmonary vascular resistance resulting in increased right to left shunt. It has a slow onset of action, prolonged effect and a failure rate as high as 29%. Tarndrup et al reported 19 +- 15 hours to regain normal behaviour. Restlessness and respiratory depression is common with DPT. In 1985 Nahata7 reported 4% incidence of life threatening complications. Snodgrass10 called for "rational and safe alternatives" in 1989. The American academy of Pediatrics Committee on drugs, issued a critical re-appraisal of lytic cocktail11 in 1995. Later significant respiratory depression, prolonged sedation were also mentioned by other investigators. In 1987 Mario et al showed significant variation in percent haemoglobin-oxygen saturation pertaining to DPT mixture.12

In 2000, Auden et al13 compared intramuscular DPT with oral ketamine/midazolam in 51 children having cardiac catheterization, ages 9 months to 10years. They claimed oral Ketamine/midazolam is better tolerated and provides superior sedation, less respiratory depression and stable haemodynamics. With the introduction of new and safer drugs in anaesthesia practice, DPT use has been declined significantly during the last two decades.

Ketamine:

Ketamine has been widely used in anaesthetic practice for about 4 decades in a variety of cases. It was first used for cardiac catheterization in 1971.14

The combination of sedation and analgesia with the maintenance of respiratory drive and airway reflexes makes it a preferable choice outside the main operating room. The increase in heart rate helps to maintain rate dependent cardiac output in paediatric group.

Despite of its well known side effects i.e. increase in salivation, emergence delirium, delayed awakening and non purposeful movements, tachycardia, hypertension and tendency to increase pulmonary vascular resistance, it remained the drug of choice for sedating children for cardiac catheterization,15 radiological procedures,16 procedural sedation in Emergency department and burns dressings.17

After the initial bolus of 1-2 mg/kg IV slowly over 3-5 minutes, an infusion of 25-100 u/kg/min has been used by many investigators.18 In a retrospective review of interventional cardiac procedures in 107 children, an increase in heart rate and mean arterial pressure by more than 20% from baseline values were seen in 10 and 9 patients. Transient apnoea and excessive salivation were seen in two patients each. Excessive movement of extremities was seen in six patients.19

In a comparative study of propofol and ketamine infusion for cardiac catheterization procedure Oklu et al20 found a decrease in systemic vascular resistance with propofol leading to increased right to left shunting, whereas ketamine did not produce these changes.

Ketamine combined with propofol and midazolam not only reduces the involuntary movements but also preserves better haemodynamics without affecting the recovery.21

Propofol:

Propofol (2,6,-diisopropylphenol) is structurally unrelated to other sedative hypnotic agents which has rapid onset, predictable level of sedation, rapid recovery and a low incidence of nausea and vomiting with minimal adverse effects. Although propofol was licensed by the Food and Drug Administration for use in children greater than 3 years of age only, the efficacy and safety of Propofol in children has been reported by several investigators.22,23

It has been used widely to provide deep sedation in the children for cardiac catheterization in a dose 1.5-2.5 mg/kg as a slow bolus over 30-60 seconds followed by 50-200 ug/kg/min infusion. It decreases the blood pressure and heart rate by 10-30 % and systemic vascular resistance by 15-20 % which can have serious consequences in patients with severe aortic stenosis, cyanotic heart disease and compromised myocardial function.

Although many investigators have reported a decrease in systemic vascular resistance and increase in right-to-left shunting with propofol.20,24 Gozal et al reported an insignificant change of intracardiac shunt with its use.14

Combination of propofol and ketamine has been used by several investigators with satisfactory results. Kogan et al25 used a mixture of propofol (4 mg/mL) and ketamine (2 mg/mL) in 45 patients aged 6 months to 16 years undergoing cardiac catheterization. They experienced 20% change in heart rate in 4 patients and blood pressure in 5 patients, whereas only 3 patients desaturated due to hypoventilation that required manual assistance of ventilation. No major complications occurred in this study. Similarly Akin et al22 used propofol (5 mg/mL) and ketamine (1 mg/ml) solution at a rate of 0.5 ml/kg in 60 children undergoing cardiac catheterization. In this study 20% decrease in blood pressure and heart rate, requirement of additional doses of propofol and fentanyl were significantly less than the control group.

In 2007, Gayatri et al26 used two doses of ketamine 12.5ug/kg/min and 25ug/kg/min with fixed dose of propofol (25ug/kg/min). They found both combinations efficacious, safe and good option in paediatric group under going cardiac catheterization.

Dexmedetomine:

Dexmedetomidine is a unique and selective a 2-adrenoceptor agonist, which inhibits neuronal firing in the brain and spinal cord resulting in hypotension, bradycardia and sedation.27

Presynaptic stimulation of a 2 receptors in the spinal cord increases the release of norepinephrine which is responsible for its analgesic effect. It possesses a biphasic haemodynamic response (high, then low) for BP and vascular resistances which results from direct activation of a 2 receptors in the vascular smooth muscles.28 Senzaki et al29 claimed dexmedetomidine a better option for sedation in TOF patients (particularly small infants) with hypercyanotic spells. Large doses of dexmedetomidine causes vasoconstriction by activating these receptors in peripheral blood vessels which results in systemic and pulmonary hypertension. There is also an increased incidence of bradycardia and atrioventricular blocks. Dexmedetomidine does not depress respiratory drive and provides a dry oral field because of its antisialogogue property.

Dexmedetomidine is currently approved by US FDA only for the sedation of intubated and mechanically ventilated adults in the intensive care unit.30 However, it has been used for paediatrics sedation in cardiac catheterization,21 radiological procedures,31 dental procedures32 and mechanical ventilation for ICU patients.33 It has also been used to control withdrawal symptoms of opioids and benzodiazepines as well as for the prevention of emergence delirium after general anaesthesia.

Although the current literature lacks dose response guidelines but investigators have used it in a dose of 0.2 to 0.75ug/kg/h in various paediatric case reports.34,35

Munro et al27 used a loading dose of 1 microg x kg(-1) dexmedetomidine administered over 10 min followed by an infusion rate of 0.5-2 ug x kg(-1) x h(-1). In this study of 20 patients heart rate and blood pressure remained within 20% of baseline. None of their patients developed significant bradycardia or hypotension. They found dexmedetomidine, a suitable alternative for sedation in spontaneously breathing patients undergoing cardiac catheterization.

Mester et al18 found combination of ketamine and dexmedetomidine as an effective means for paediatric sedation in cardiac catheterization procedures.

On the contrary, Tosun et al21 found the propofol-ketamine combination superior to a combination of dexmedetomidine-ketamine which not only produced insufficient sedation and analgesia but also resulted in a longer recovery time.

Benzodiazepines:

Since benzodiazepines lack any analgesic effects, therefore they are used with ketamine or opioids. The combination of benzodiazepines with Ketamine not only reduces its emergence delirium but also provide better sedation and amnesia. Midazolam is the most commonly used benzodiazepine because of its shorter duration of action and inactive metabolites. Benzodiazepines produce dose-dependent respiratory depression, which is more marked in patients with respiratory disease, congenital heart disease and when combined with opioids.

Opioids:

Very few studies are available regarding the use of opioids during cardiac catheterization. In different studies Rautiainen36,37 described the use of fentanyl and alfentanil as an effective method of sedation in catheterization lab. Because of their well known respiratory depression, they are generally used in conjunction with benzodiazepine or propofol. Newer opioids like fentanyl, alfentanil and remifentanil have rapid onset of action, shorter duration and provide better haemodynamics stability.

Conclusion

A variety of drugs regimens can be used for the cardiac catheterization procedures in children with congenital heart disease. A good preoperative assessment, thorough understanding of the disease and the procedure to be performed enable the anaesthesiologist to choose and use the right drug regimen for a safe anaesthetic management. Ketamine with or without benzodiazepines has remained the drug of choice for about 4 decades. Propofol with ketamine has provided near to ideal combination to provide deep sedation with adequate analgesia and stable haemodynamics in a spontaneously breathing patient.

Reference

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(Department of Cardiac Anaesthesia and Intensive Care Units, Prince Sultan Cardiac Center, Riyadh, Kingdom of Saudi Arabia.)
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Geographic Code:9PAKI
Date:Feb 29, 2012
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