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Peter Houtman
Children’s Hospital, Leicester Royal Infirmary, Leicester, UK Email: peter.houtman@uhl-tr.nhs.uk
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Paediatric and Perinatal Drug Therapy, 2003; 5 (3)
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Paediatric and Perinatal Drug Therapy, 2003; 5 (3)
Table 2. Drug doses for hypertensive emergencies (start with the lower doses)
Drug Route Dose
Sodium nitroprusside IV 0.5–8 microg/kg/min
Labetalol IV 0.25–1.5 mg/kg/hr
Nifedipine Oral 0.1–0.25 mg/kg/dose (initial doses)
Nicardipine IV 1–3 microg/kg/min
Diazoxide IV 1–3 mg/kg/dose
arteries). Visual loss may be permanent. Thus, blockade but there is also a-adrenergic blockade
the principle of slow reduction of severe, chronic (15%). It therefore reduces cardiac output and
hypertension is paramount. causes peripheral vasodilatation. It has a rapid
onset but a longer duration of action (hours) and
Drug therapy is therefore not capable of such sensitive BP
regulation as nitroprusside. Its use is limited if
The specific drugs most widely recommended for there is clinical evidence of cardiac failure as it
initial emergency management are sodium may further lower cardiac output. Like other
nitroprusside and labetalol. Other drugs that have b-blockers, there must be caution in asthmatics.
also been recommended include nifedipine, It is metabolised in the liver and its use is not
nicardipine and diazoxide. These are discussed limited in renal failure. Initial incremental loading
individually below, and doses are given in Table doses of 250 microg/kg (up to 1 mg/kg) have
2. However, whichever drug is used, the principle been recommended followed by an infusion of
of the slow reduction in blood pressure is the same. 0.25–1.5 mg/kg/h13.
A helpful goal to strive for is to aim to reduce BP
initially by only a third of the difference between Nifedipine
the acute BP level and the appropriate normal The use of nifedipine in the acute phase is
value. Only after the first 24 hours or more should controversial14. In adults, its use has been
it be attempted to reduce BP further with the associated with extreme hypotension and
gradual addition of longer-acting drugs. Whichever neurological effects. However, in children this has
agent is used, frequent and reliable BP monitoring rarely been reported and a recent series endorses
is necessary. An intravenous saline infusion should
its safety in children when used appropriately15.
be available to raise BP if it has dropped too low.
Its action is by vasodilatation. Cardiac output is
maintained but there is often a reflex tachycardia,
Sodium nitroprusside which in adults certainly may lead to myocardial
Sodium nitroprusside is a potent vasodilator with
or cerebral ischaemia. Headaches and flushing are
an almost instant effect when given intravenously.
common. Many paediatric centres use this drug
It is also very short-acting (seconds) and therefore
in an otherwise well child and in small, frequent
capable of exquisite BP control. Continuous BP
doses (initially 100–250 microg/kg). Subsequently
monitoring is mandatory. The drug undergoes
rapid photo-degradation so the solution must be larger doses may be appropriate, when the child
covered with aluminium foil. In vivo, cyanide is has demonstrated that initial doses have not caused
produced from its local breakdown in smooth a precipitate drop in BP. Small doses can be
muscle, which is then metabolised to thiocyanate extracted from the capsules and the effect can be
in the liver. This is excreted by the kidney. quite rapid, starting within 10 minutes.
Therefore it must be used with caution in patients Unfortunately with the difficulty in accurately
with renal or hepatic failure. In the absence of measuring the small doses of liquid from the
organ failure, a clinical problem should not be capsules, dosing errors may occur and care needs
expected unless the drug is used for more than to be taken16. The duration of effect and potency
48 hours or so. After this time a worsening when used in this way is unpredictable,
metabolic acidosis can be anticipated. It may be particularly when absorption is variably sublingual
possible to measure thiocyanate levels in these and from the stomach and small bowel, but the
circumstances, but usually the patient will be longer-acting (sustained-release) preparations are
suitable for longer-acting drugs by this time. not suitable in the immediate emergency situation.
Unfortunately nifedipine in this context illustrates
Labetalol the difficulty in administering medicines in small
Labetalol is also commonly used in the acute doses to children when the formulations available
situation. Most of its action is via b-adrenergic are really suitable only for larger individuals.
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Paediatric and Perinatal Drug Therapy, 2003; 5 (3)
Nicardipine References
Recently an intravenously administered calcium-
channel antagonist, nicardipine, has become 1. Jones DW, Frohlich ED, Grim CM, Grim CE,
available. Although there is limited experience Taubert KA. Mercury sphygmomanometers should
with its use in paediatric practice, reports of its not be abandoned: An advisory statement from
the Council for High Blood Pressure Research,
suitability have been favourable17, and it is American Heart Association. Hypertension
increasingly being used for children. It has a very 2001;37:185–186.
rapid onset of action, within a few minutes, and 2. National High Blood Pressure Education Program
a relatively short duration of action (half-life 40 Working Group on Hypertension Control in
minutes). Advantages over nitroprusside include Children and Adolescents. Update on the 1987
the ability to use it for more than a few days, as Task Force Report on High Blood Pressure in
Children and Adolescents: a Working Group Report
it does not produce toxic metabolites. In a recent
from the National High Blood Pressure Education
study18, when used in doses gradually increasing Program. Pediatrics 1996;88:649–658.
to 3 microg/kg/min, nicardipine only occasionally 3. Mentser M, Bunchman T. Nephrology in the
caused unwarranted hypotension and this was paediatric intensive care unit. Semin Nephrol
readily improved by stopping the drug. 1998;18:330–340.
Intravenous calcium can also be used in situations 4. National Heart, Lung, and Blood Institute. Report
of hypotension and reduced cardiac output (0.2 of the Second Task Force on Blood Pressure Control
in Children. Pediatrics 1987;79:1–25.
ml/kg i.v. in the form of 10% calcium chloride 5. Groshong T. Hypertensive crisis in children. Pediatr
over 5 minutes)19. Ann 1996;25:368–371, 375–376.
6. Adelman RD, Coppo R, Dillon MJ. The emergency
Diazoxide management of severe hypertension. Pediatr
For many years, diazoxide was the most Nephrol 2000;14:422–427.
frequently used drug for hypertensive 7. Fivush B, Neu A, Furth S. Acute hypertensive
crises in children: emergencies and urgencies. Curr
emergencies. Its use has decreased as other drugs Opin Pediatr 1997;9:233–236.
have become available. It has unpredictable 8. Feld LG, Waz WR. Treatment of hypertension. In
potency and is associated with the complications Ed. Barratt TM, Avner ED and Harmon WE.
relating to over-rapid reduction of blood pressure. Pediatric Nephrology. 4th ed. Baltimore: Lippincott,
However, it still can be useful if used in small, Williams and Wilkins. 1999:1031–1049.
frequent doses (1–3 mg/kg/dose) rather than the 9. Deal JE, Barratt TM, Dillon MJ. Management of
hypertensive emergencies. Arch Dis Child
large boluses employed in the past. There is a
1992;67:1089–1092.
risk of hyperglycaemia and a maximum total dose 10. Houtman PN, Shah V, Barratt TM, Dillon MJ.
of no more than 10 mg/kg per 24 hours is Reduction of hypertension in hypovolaemia.
generally recommended. Lancet 1990;336:1454.
11. Proulx F, Lacroix J. Farrell CA. Gauthier M.
Other drugs Convulsions and hypertension in children:
differentiating cause from effect. Crit Care Med
Intravenous hydralazine is no longer indicated in
1993;21:1541–1546.
the emergency situation now that drugs with 12. Houtman PN, Dillon MJ. Medical management of
more predictable potency and fewer side effects hypertension in childhood. Child Nephrol Urol
are available. Mention should be made of the 1992;12:154–161.
ACE-inhibitors so as to emphasise that they are 13. Bunchman TE, Lynch RE, Wood EG. Intravenously
not usually suitable for use in an emergency – administrated labetalol for treatment of hypertension
the magnitude of their effect is dependent on in children. J Pediatr 1992;120:140–144.
14. Sinaiko AR, Daniels SR. The use of short-acting
renin-status and they are particularly potent in nifedipine in children with hypertension: Another
renovascular disease. Their effects are therefore example of the need for comprehensive drug
unpredictable, particularly if the cause of the testing in children. J Pediatr 2001;139:7–9.
hypertension is unknown. In unilateral renal 15. Blaszak RT, Savage JA, Ellis EN. The use of short-
vascular disease there is the very real risk of acting nifedipine in pediatric patients with
infarction of the affected kidney. hypertension. J Pediatr 2001;139:34–37.
16. Flynn JT. Nifedipine in the treatment of
hypertension in children. J Pediatr
In the second phase of management there is 2002;140:787–788.
gradual reduction of short-acting drugs and 17. Michael J, Groshong T, Tobias JD. Nicardipine for
gradual introduction of oral longer-acting drugs. hypertensive emergencies in children with renal
At this stage, it is still important not to reduce disease. Pediatr Nephrol 1998;12:40–42.
BP too quickly. Usually more than one drug is 18. Flynn, JT, Mottes TA, Brophy PD, Kershaw DB,
Smoyer WE, Bunchman TE. Intravenous
used, for example a b-blocker, diuretic and
nicardipine for treatment of severe hypertension
vasodilator. Success depends on a good knowledge in children. J Pediatr 2001;139:38–43.
of the treatment of hypertension generally and 19. Kenny J. Treating overdose with calcium channel
will usually require an appropriate specialist. blockers. BMJ 1994;308:992–993.
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