chiara.qxp 4/7/08 10:00 am Page 111
Congenital Heart Surgery
Vasopressin in the Treatment of Anaphylactic Shock in
Paediatric Congenital Heart Surgery
a report by
Luca Di Chiara
Department of Paediatric Cardiology and Cardiac Surgery, Bambino Gesù Hospital, Rome
Anaphylaxis is clinically defined as a severe systemic allergic reaction of administration, as demonstrated by the vasoconstrictive effects and
rapid onset, the hallmarks of which are acute cardiovascular and reduction in the inotropic requirements of inhibitors of NO synthesis.
pulmonary dysfunction. In anaesthetics the incidence of this severe These vasodilating and negative inotropic effects are mediated by NO-
complication is between 1:5,000 and 1:25,000, and it is one of the few sustained myosin dephosphorylation and, as mentioned above, by the
remaining causes of mortality directly due to general anaesthesia. During activation of the K
ATP
and K
Ca
of the vascular smooth-muscle membrane.
cardiac surgery, children are exposed to multiple foreign substances that
have the potential to induce a life-threatening allergic reaction. The most Deficiency of the Vasopressin Hormone
frequent agents involved are antibiotics, neuromuscular blocking agents, Finally, both prolonged low systemic hypoperfusion with tissue hypoxia
blood and blood products, intravascular volume expanders, polypeptides and lactic acidosis can be the cause of all of the described
and, more rarely, heparins.
1
pathophysiological mechanisms, and can induce a relative deficiency in
vasopressin plasma concentration, which further amplifies the vasoplegic
Pathophysiology scenario.
5
As well as the NO release at the posterior pituitary gland, several
Cardiovascular collapse due to anaphylaxis is a vasodilatory shock other mechanisms can be involved in inappropriately low vasopressin
characterised by vasodilatation, enhanced vascular permeability and concentrations, such as exhaustion of the pituitary stores, autonomic
intravascular volume depletion. Multiple mediators from mast cells such as dysfunction and the inhibitory effect of the increased norepinephrine
kinins, leukotrienes and prostanoids are implicated in promoting concentrations. The inappropriately low plasma vasopressin concentration
vasodilatation, but histamine seems to play a very important role.
2
Despite is the third main pathophysiological mechanism of vasodilatory shock, a
a few studies suggesting an alteration of myocardial contractility
3–5
and the finding that has been proved in septic shock, haemorrhagic shock
presence of histamine receptors
6,7
in the heart, cardiac abnormalities during unresponsive to volume replacement and catecholamine administration
anaphylactic shock are usually due to an underlying cardiac disease or the and vasodilatory shock after cardiopulmonary bypass.
side effects of catecholamines administered rather than the anaphylaxis
itself.
8
Despite the existence of different pathogenetic mechanisms Treatment of Anaphylactic Shock
characterising various forms of vasodilatory shock, common mechanisms of The most important requirements in the treatment of anaphylaxis are
vasodilation and catecholamine resistance have been demonstrated, such prompt diagnosis and the maintenance of coronary and cerebral perfusion.
as activation of the adenosine-5’-triphosphate (ATP)-sensitive potassium The underlying congenital heart disease makes the patient extremely
channels (K
ATP
channels), activation of the inducible form of nitric oxide intolerant to the adverse cardiocirculatory effects of anaphylactic shock;
(NO) and deficiency of the vasopressin hormone. nevertheless, in the presence of physicians skilled in the rapid diagnosis and
management of acute cardiovascular dysfunction and with the patient
Activation of the ATP-sensitive Potassium Channels in the haemodynamically monitored, any adverse events that take place in the
Plasma Membrane of the Vascular Smooth Muscle operating theatre can be quickly diagnosed and immediately treated.
The K
ATP
channels exert a central role in regulating the resting The cornerstone of treatment is airway maintenance with 100% oxygen
potential of vascular smooth muscle membrane. These channels are and intravascular volume expansion, the latter being effectively guided
physiologically closed in their inactive form. Two mechanisms by transoesophageal echocardiography. Epinephrine has been widely
are involved in their activation and opening: a fall of the intracellular pH due accepted as being the standard medical therapy to reverse cardiovascular
to low ATP concentration and increasing hydrogen ions and lactate levels
9,10
collapse and bronchospasm in anaphylaxis.
13
As a last resort, a rapid
(a mechanism that links cellular metabolism with vascular tone and blood placement onto cardiopulmonary bypass with a perfusion strategy based
flow),
11
and NO release through the cyclic guanosine monophosphate on high flow in moderate hypothermia with a normal haematocrit value
(cGMP)-dependent mechanisms.
12
The K
ATP
opening results in K efflux, may help to achieve a positive final outcome by maintaining adequate end-
cellular hyperpolarisation, closure of the voltage-gate calcium channels and organ perfusion while adjusting the pharmacological treatment.
14
Second-
intracytosolic calcium decrease with a final vasodilatory effect. This impaired line treatment consists of corticosteroids, which may have value in the early
free calcium movement through the sarcolemma further contributes to the hours of any post-resuscitation period, and β2 agonists (terbutaline or
catecholamine resistance characteristic of vasodilatory shock. albutenol) administered by inhalation via the endotracheal tube in order to
treat bronchospasm. Epinephrine administration is the first-line treatment
Activation of the Inducible Form of Nitric Oxide for anaphylactic shock, regardless of the existence of human studies that
Stimulation of H1 receptors on endothelium cells activates both NO- and are not entirely supportive of its use.
15,16
In fact, there are strong
prostacycline-mediated vasodilating pathways. NO overexpression pathophysiological findings sustaining its efficacy: due to its α- and
contributes to vasodilatation and poor sensitivity to catecholamine β-adrenergic effects, epinephrine inhibits further vasodilating mediator
© TOUCH BRIEFINGS 2008 111
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