NITROGLYCERIN (TNG) (2,6)
Niroglycerin is organic nitrate that acts principally on venous capacitance vessels to produce peripheral pooling of blood,reduction of heart size and decreased cardiac ventricular wall tension. Continuous intravenous infusion of TNG via special delivery tubing to reduce absorbtion of the drugs into plastic,is an ideal approach to maintain a constant plasma concentration of TNG.
TNG induced venous dilatation and increased venous capacitance,decreases venous return to the heart(e.g.preload)resulting in reduced ventricular and diastolic pressure and volume and therefore decreases myocardial oxygen requirement (Greenberg et al 1975).
In addition any drug induce reduction in peripheral vascular resistance decreases myocardial oxygen requirements.
TNG can be used to produce controlled hypotension but is less potent than SNP. For example equivalent reduction in blood pressure((BP) are achieved by continuous
intravenous infusion of TNG 4,7 mcg/kg/min,and SNP
2,5 mcg/kg/min,(Fahmy,1978).
Because TNG acts predominantly on venous capacitance vessels, the production of control hypotension using this drug may be more dependent on intravascular fluid volume as compared with SNP.
In the otherhand TNG might be reasonable choice if mild hypotension is absolutely required in patient with known significant coronary artery disease.
Continuous intravenous infusion of TNG,0,25 to 1 mcg/kg
/min,has been utilized intraoperatively as a prophylaxis against myocardial ischemia in anesthetized patients with known coronary artery disease (Kaplan et al 1976).
TNG primarily dilates larger conductance vessels of the coronary circulation often leading to an increase in coronary blood flow to ischemic subendocardial areas.In contrast SNP may produce a coronary steal phenomena.
Indeed the frequency of ST segment elevation during acute coronary occlusion in dogs is reduced by TNG but increased by SNP(Chiariello et al 1976).
For these reasons,TNG has been recomended infavor of SNP for the treatment of hypertension in patients with coronary artery disease (Kaplett 76).
TNG does, however reduce the incidence of hypertension as may occur during direct laryngoscopy and intubation of the trachea. Like SNP,TNG is cerebral vasodilator and may increase intracranial pressure (ICP) in patients with decreased intracranial compliance (Gagnon et al 1971).
However, the increase in ICP produced by TNG may be even greater than with SNP.
Recovery from TNG induced hypotension is also less rapid taking between 10-20 minutes in contrast to the 2-4 minutes with SNP.
The nitrite metabolic of NTG is capable converting hemoglobin to methemoglobin.
Although significant formation is unlikely with total TNG doses less than 5 mg/kg.
TRIMETHAPHAN :(1,6)
A peripheral vasodilator and ganglionic blocker that acts rapidly but so briefly that it must be given by continuous intavenous(iv) infusion.
Trimethaphan is most often used as a continuous iv infusion (10-200 mcg/kg/min),to produce controlled hypotension.
Trimethaphan is shorter acting,reversal of hypotension takes place in 10-30 minutes.The mechanism for its action is probably the rapid excretion of 30% of drug in the urine.
Dose 0,1% solution(1mg/ml or 500mg/500 ml)in 5% D/W as iv drip infusion. The level of BP must be correlated with the vascular ooze then maintained.
Try not to let BP get down below 80-90 torr, if at all possible to diminish post operative complications.
In ASA class I patients, a fall to 70 torr may be permissible.
Trimethaphan induced hypotension in animals is associated with decreased coronary blood flow, but unchanged renal and hepatic blood flow. Evokes smaller increases in ICP than associated with comperable degree of hypotension produced by SSNP or TNG (Turner et al 1977).
Tachycardia may accompany drug induced reduction in BP, and cardiac output is likely as a manifestation of decreased venous return.
Its side effect are mydriasis,reduced gastrointestinal activity culminating in ileus and urinary retention.
Mydriasis may interfere with neurologic evaluation of the patient following intracranial surgery.
Histamin release that may be accompany the administra-
tion of trimethaphan therefore should be avoided in patients with allergies.
It is a potent inhibitor of plasma choline esterase such that the duration of action of succynilcholine is likely to be prolonged.(Sklar and Lanks 1977).
BETA ADRENOCEPTOR BLOCKADE :(2)
The main advantage of the beta receptor antagonist (beta blocker) in induced hypotension are in the reduction of heart rate and cardiac output.
Many anesthetist believe that the maintanance of slow heart rate without any additional hypotension considerably reduce operative bleeding.
Although preoperative oral therapy with propranolol (40 mg tds)is probably best,1-2 mg intravenously can be used during anesthesia.
Beta adrenergic blockade with propranolol or oxprenolol is also employed either preoperatively.
Intravenous administration of labetalol (20-40)mg over 2 minutes produces reduction in BP because of simultanous decreases in cardiac output and peripheral vascular resistance.
The prompt reduction in BP produced by iv labetalol make this a useful drug in the treatment of hypertensive emergencies and production of controlled hypotension (Morel et al 1982).
Both labetalol and esmolol,a beta adrenergic blocking drug with a half life of 9 minutes are indeed useful by themselves or as adjuncts for induced hypotension because they do not cause cerebral vasodilatation,
tachycardia or rebound hypertension, but suffering from lack of potency and is expensive.
Beta blockers may also increase the tendency to hypogly-
caemia in insulin dependent diabetics and combination of hypoglycaemia plus hypotension can produce severe consequences, particularly on cerebral metabolism.
Side effect of labetalol is orthostatichypotension,brady
cardia,fluid retention diarrhae,nausea,fatigue and dryness of the mouth.
Hexamethonium: long acting(1,2)
Acts on synaptic transmission in autonomic ganglia(sympa-
thetic and parasympathic)by increasing the thresold of ganglion cells for acetylcholine.
Excreted unchanged by kidney,accumulates in kidney failure. Coronary blood flow increases slightly and coronary vascular resistance is decreased and splanchnic blood flow is decreased but there is no change in splanchnic vascular resistance.
Impair stress reduced gluconeogenesis mediated by adrenaline by producing sympathetic blockade.
ISOFLURANE :
Isoflurane lowers the BP through peripheral vasodilatation when compared with SNP isoflurane attenuates the stress response to induced hypotension.
Although the use of isoflurane has been associated with exacerbation of ST segment changes and the shunting of blood from regions of myocardium dependent on collateral circulation,there is no increase in pulmonary shunting or dead space with isoflurane induced hypotension.
Isoflurane reduces the cerebral metabolic rate(CMR) and maintanance cerebral blood flow(CBF) but at clinical doses isoflurane conferless protection than thiopenthal in a vitro hyppocampal slice model.
Even in the presence of mild hypothermia, isoflurane did not give greater cerebral protection than halothane in a rat model of focal ischemia. Since isoflurane interference with cardiac output and autoregulation is dose related combining isoflurane with either labetalol,an alpha and beta blocking drug or enalapril, an angiotension conver
ting enzyme inhibitor, will facilitate the achievement of adequate levels of hypotension with less 1% isoflurane.
Often a combination of agents will allow the need level of hypotension to be reached which avoiding large doses of any particular agent thus reducing side effects and expence.
Isoflurane offers the advantage of preservation of cardiac output and mild vasodilatation, short duration of action and some reduction in cerebral and spinal ischemic insult.
COMPLICATIONS :(1)
Induced hypotension can be the cause of morbidity and mortality :
1.The most common complications:
a.Cerebral thrombosis and hypoxia.
b.Reactionary hemorrhage.
c.Oliguria,anuria,renal failure.
d.Coronary thrombosis,heart failure and arrest.
e.Thrombo embolic phenomena.
f. Persistent hypotension.
g.Delayed awakening.
2.The incidence of complications has been decreasing as
anesthesiologist gain experience with this technique.
Use of vasopressors: two points of view.(1)
1.Some state that the BP should not be allowed to re-
turn to preoperative levels prior to wound closure so
that bleeders may be ligated or cauterized.
2.However,there is another point of view :
Administration of vasopressors is contrary to the
expressed purposed of induced hypotension clots
form in the dilated vessels.
When reversal of the hypotension is proceding,
the vein contract as the form clots.The vasopressor
might dislodge the clot and cause bleeding.
POST OPERATIVE MANAGEMENT:(2)
Recovery staff must be made aware in whom elective hypotension has been employed. Accurate and frequent monitoring of BP together with airway care to prevent obstruction and CO2 retention are essential particularly if the patient is still deeply anesthetized.
The patient's position should be determined by BP measured and postural changes may be necessary for several hours to ensure adequate cerebral perfusion.
Supplementary oxygen should be administered in all cases until the patient is adequately awake, and may be required for longer where oxygenation is thought to be critical.
In cases where pharmacoligical modification of sympathe
tic responses has been undertaken,such as with the use of ganglionic blocking drugs, patient should remain in bed for 12-18 hours post operatively.If necessary lying virtually flat until they are able to sit up without filling dizzy.
SUMMARY :
Induced hypotension technique can be effective when indicated and carefully conducted, although this method is potentially dangerous therefore before selecting this method one must be sure the advantages outweight the disasvantages following thorough review of all the facts.
Proper selection and positioning of the patient,careful monitoring, an experienced anesthesiologist and skillful surgeon, and excellent pre and post operative care must be prepared.
Induced hypotension increases slack in the structures around the aneurysm and aneurysmal sac and decreases of the risk of rupture during surgical dissection and clipping of the anaurysm decreases bleeding from surrounding small vessels which allows better visualization of the anatomy of aneurysm and perforating vessels but there are numerous problems associated with it, such as impaired autoregulation,cerebral vasopasm and hypoten-
sion may therefore lead to focal or global cerebral ischemia and furthermore the ischemic thresold cannot be predicted accurately.
REFERENCES :
1.Snow J.C : Hypotension technique and Induced hypo
thermia: Manual of Anesthesia;first edit. Little Brown
and Company,Boston,Tokyo 1977,pp.239-45.
2.Simson J.P: Blood loss and its reduction;Nun F.J.,Utting
EJ,Brown RB: General Anesthesia;fifth edith,Butter
worths,London,Boston,Sidney,1989,pp 566-9.
3.Bogdouff : Anesthesia for intracranial vascular surgery;
Stone JD,Sperry JR:The neuro Anesthesia Handbook,
Mosby,St.Lousi,Baltimore Boston,1996,pp.346-7.
4.Godsiff SL : Anesthesia for intracranial vascular surgery;
Matta.FB,Menon KD:neuroanesthesia and Critical Care;
first edit.Greenwich Medical Media Ltd,2000.pp208-11.
5.Weir K.B: Intracranial Aneurysms and AV Malformation,
Surgical Consideration; Albin S Maurice:Neuroanesthesia
with Neurosurgical and Neuroscience Perspective;
Mc Graw Hill Companies, USA,1997.pp.877-8.
6.Stoelting KR:Peripheral Vasodilators;Pharmacology and
Physiology in Anesthetic Practice;J.B.Lippincott Compa-
Company;Philadelphia,1987.pp.307-17.
Niroglycerin is organic nitrate that acts principally on venous capacitance vessels to produce peripheral pooling of blood,reduction of heart size and decreased cardiac ventricular wall tension. Continuous intravenous infusion of TNG via special delivery tubing to reduce absorbtion of the drugs into plastic,is an ideal approach to maintain a constant plasma concentration of TNG.
TNG induced venous dilatation and increased venous capacitance,decreases venous return to the heart(e.g.preload)resulting in reduced ventricular and diastolic pressure and volume and therefore decreases myocardial oxygen requirement (Greenberg et al 1975).
In addition any drug induce reduction in peripheral vascular resistance decreases myocardial oxygen requirements.
TNG can be used to produce controlled hypotension but is less potent than SNP. For example equivalent reduction in blood pressure((BP) are achieved by continuous
intravenous infusion of TNG 4,7 mcg/kg/min,and SNP
2,5 mcg/kg/min,(Fahmy,1978).
Because TNG acts predominantly on venous capacitance vessels, the production of control hypotension using this drug may be more dependent on intravascular fluid volume as compared with SNP.
In the otherhand TNG might be reasonable choice if mild hypotension is absolutely required in patient with known significant coronary artery disease.
Continuous intravenous infusion of TNG,0,25 to 1 mcg/kg
/min,has been utilized intraoperatively as a prophylaxis against myocardial ischemia in anesthetized patients with known coronary artery disease (Kaplan et al 1976).
TNG primarily dilates larger conductance vessels of the coronary circulation often leading to an increase in coronary blood flow to ischemic subendocardial areas.In contrast SNP may produce a coronary steal phenomena.
Indeed the frequency of ST segment elevation during acute coronary occlusion in dogs is reduced by TNG but increased by SNP(Chiariello et al 1976).
For these reasons,TNG has been recomended infavor of SNP for the treatment of hypertension in patients with coronary artery disease (Kaplett 76).
TNG does, however reduce the incidence of hypertension as may occur during direct laryngoscopy and intubation of the trachea. Like SNP,TNG is cerebral vasodilator and may increase intracranial pressure (ICP) in patients with decreased intracranial compliance (Gagnon et al 1971).
However, the increase in ICP produced by TNG may be even greater than with SNP.
Recovery from TNG induced hypotension is also less rapid taking between 10-20 minutes in contrast to the 2-4 minutes with SNP.
The nitrite metabolic of NTG is capable converting hemoglobin to methemoglobin.
Although significant formation is unlikely with total TNG doses less than 5 mg/kg.
TRIMETHAPHAN :(1,6)
A peripheral vasodilator and ganglionic blocker that acts rapidly but so briefly that it must be given by continuous intavenous(iv) infusion.
Trimethaphan is most often used as a continuous iv infusion (10-200 mcg/kg/min),to produce controlled hypotension.
Trimethaphan is shorter acting,reversal of hypotension takes place in 10-30 minutes.The mechanism for its action is probably the rapid excretion of 30% of drug in the urine.
Dose 0,1% solution(1mg/ml or 500mg/500 ml)in 5% D/W as iv drip infusion. The level of BP must be correlated with the vascular ooze then maintained.
Try not to let BP get down below 80-90 torr, if at all possible to diminish post operative complications.
In ASA class I patients, a fall to 70 torr may be permissible.
Trimethaphan induced hypotension in animals is associated with decreased coronary blood flow, but unchanged renal and hepatic blood flow. Evokes smaller increases in ICP than associated with comperable degree of hypotension produced by SSNP or TNG (Turner et al 1977).
Tachycardia may accompany drug induced reduction in BP, and cardiac output is likely as a manifestation of decreased venous return.
Its side effect are mydriasis,reduced gastrointestinal activity culminating in ileus and urinary retention.
Mydriasis may interfere with neurologic evaluation of the patient following intracranial surgery.
Histamin release that may be accompany the administra-
tion of trimethaphan therefore should be avoided in patients with allergies.
It is a potent inhibitor of plasma choline esterase such that the duration of action of succynilcholine is likely to be prolonged.(Sklar and Lanks 1977).
BETA ADRENOCEPTOR BLOCKADE :(2)
The main advantage of the beta receptor antagonist (beta blocker) in induced hypotension are in the reduction of heart rate and cardiac output.
Many anesthetist believe that the maintanance of slow heart rate without any additional hypotension considerably reduce operative bleeding.
Although preoperative oral therapy with propranolol (40 mg tds)is probably best,1-2 mg intravenously can be used during anesthesia.
Beta adrenergic blockade with propranolol or oxprenolol is also employed either preoperatively.
Intravenous administration of labetalol (20-40)mg over 2 minutes produces reduction in BP because of simultanous decreases in cardiac output and peripheral vascular resistance.
The prompt reduction in BP produced by iv labetalol make this a useful drug in the treatment of hypertensive emergencies and production of controlled hypotension (Morel et al 1982).
Both labetalol and esmolol,a beta adrenergic blocking drug with a half life of 9 minutes are indeed useful by themselves or as adjuncts for induced hypotension because they do not cause cerebral vasodilatation,
tachycardia or rebound hypertension, but suffering from lack of potency and is expensive.
Beta blockers may also increase the tendency to hypogly-
caemia in insulin dependent diabetics and combination of hypoglycaemia plus hypotension can produce severe consequences, particularly on cerebral metabolism.
Side effect of labetalol is orthostatichypotension,brady
cardia,fluid retention diarrhae,nausea,fatigue and dryness of the mouth.
Hexamethonium: long acting(1,2)
Acts on synaptic transmission in autonomic ganglia(sympa-
thetic and parasympathic)by increasing the thresold of ganglion cells for acetylcholine.
Excreted unchanged by kidney,accumulates in kidney failure. Coronary blood flow increases slightly and coronary vascular resistance is decreased and splanchnic blood flow is decreased but there is no change in splanchnic vascular resistance.
Impair stress reduced gluconeogenesis mediated by adrenaline by producing sympathetic blockade.
ISOFLURANE :
Isoflurane lowers the BP through peripheral vasodilatation when compared with SNP isoflurane attenuates the stress response to induced hypotension.
Although the use of isoflurane has been associated with exacerbation of ST segment changes and the shunting of blood from regions of myocardium dependent on collateral circulation,there is no increase in pulmonary shunting or dead space with isoflurane induced hypotension.
Isoflurane reduces the cerebral metabolic rate(CMR) and maintanance cerebral blood flow(CBF) but at clinical doses isoflurane conferless protection than thiopenthal in a vitro hyppocampal slice model.
Even in the presence of mild hypothermia, isoflurane did not give greater cerebral protection than halothane in a rat model of focal ischemia. Since isoflurane interference with cardiac output and autoregulation is dose related combining isoflurane with either labetalol,an alpha and beta blocking drug or enalapril, an angiotension conver
ting enzyme inhibitor, will facilitate the achievement of adequate levels of hypotension with less 1% isoflurane.
Often a combination of agents will allow the need level of hypotension to be reached which avoiding large doses of any particular agent thus reducing side effects and expence.
Isoflurane offers the advantage of preservation of cardiac output and mild vasodilatation, short duration of action and some reduction in cerebral and spinal ischemic insult.
COMPLICATIONS :(1)
Induced hypotension can be the cause of morbidity and mortality :
1.The most common complications:
a.Cerebral thrombosis and hypoxia.
b.Reactionary hemorrhage.
c.Oliguria,anuria,renal failure.
d.Coronary thrombosis,heart failure and arrest.
e.Thrombo embolic phenomena.
f. Persistent hypotension.
g.Delayed awakening.
2.The incidence of complications has been decreasing as
anesthesiologist gain experience with this technique.
Use of vasopressors: two points of view.(1)
1.Some state that the BP should not be allowed to re-
turn to preoperative levels prior to wound closure so
that bleeders may be ligated or cauterized.
2.However,there is another point of view :
Administration of vasopressors is contrary to the
expressed purposed of induced hypotension clots
form in the dilated vessels.
When reversal of the hypotension is proceding,
the vein contract as the form clots.The vasopressor
might dislodge the clot and cause bleeding.
POST OPERATIVE MANAGEMENT:(2)
Recovery staff must be made aware in whom elective hypotension has been employed. Accurate and frequent monitoring of BP together with airway care to prevent obstruction and CO2 retention are essential particularly if the patient is still deeply anesthetized.
The patient's position should be determined by BP measured and postural changes may be necessary for several hours to ensure adequate cerebral perfusion.
Supplementary oxygen should be administered in all cases until the patient is adequately awake, and may be required for longer where oxygenation is thought to be critical.
In cases where pharmacoligical modification of sympathe
tic responses has been undertaken,such as with the use of ganglionic blocking drugs, patient should remain in bed for 12-18 hours post operatively.If necessary lying virtually flat until they are able to sit up without filling dizzy.
SUMMARY :
Induced hypotension technique can be effective when indicated and carefully conducted, although this method is potentially dangerous therefore before selecting this method one must be sure the advantages outweight the disasvantages following thorough review of all the facts.
Proper selection and positioning of the patient,careful monitoring, an experienced anesthesiologist and skillful surgeon, and excellent pre and post operative care must be prepared.
Induced hypotension increases slack in the structures around the aneurysm and aneurysmal sac and decreases of the risk of rupture during surgical dissection and clipping of the anaurysm decreases bleeding from surrounding small vessels which allows better visualization of the anatomy of aneurysm and perforating vessels but there are numerous problems associated with it, such as impaired autoregulation,cerebral vasopasm and hypoten-
sion may therefore lead to focal or global cerebral ischemia and furthermore the ischemic thresold cannot be predicted accurately.
REFERENCES :
1.Snow J.C : Hypotension technique and Induced hypo
thermia: Manual of Anesthesia;first edit. Little Brown
and Company,Boston,Tokyo 1977,pp.239-45.
2.Simson J.P: Blood loss and its reduction;Nun F.J.,Utting
EJ,Brown RB: General Anesthesia;fifth edith,Butter
worths,London,Boston,Sidney,1989,pp 566-9.
3.Bogdouff : Anesthesia for intracranial vascular surgery;
Stone JD,Sperry JR:The neuro Anesthesia Handbook,
Mosby,St.Lousi,Baltimore Boston,1996,pp.346-7.
4.Godsiff SL : Anesthesia for intracranial vascular surgery;
Matta.FB,Menon KD:neuroanesthesia and Critical Care;
first edit.Greenwich Medical Media Ltd,2000.pp208-11.
5.Weir K.B: Intracranial Aneurysms and AV Malformation,
Surgical Consideration; Albin S Maurice:Neuroanesthesia
with Neurosurgical and Neuroscience Perspective;
Mc Graw Hill Companies, USA,1997.pp.877-8.
6.Stoelting KR:Peripheral Vasodilators;Pharmacology and
Physiology in Anesthetic Practice;J.B.Lippincott Compa-
Company;Philadelphia,1987.pp.307-17.
