Michael Lagerkranser

Controlled Hypotension with Adenosine in Cerebral Aneurysm Surgery

The cardiovascular effects of adenosine-induced controlled hypotension were studied in 10 patients undergoing cerebral aneurysm surgery. Adenosine and its metabolites were measured in arterial plasma using high-pressure liquid chromatography. Whole body and cerebral arteriovenous oxygen content differences (AVDO2), arterial lactate levels, and arteriojugular lactate differences were determined. In order to reduce the dose requirement of adenosine, the patients were pretreated with the adenosine uptake inhibitor, dipyridamole (0.3–0.4 mg · kg-1). During the infusion of adenosine (0.14 ± 0.04 mg · kg-1 · min-1) the mean arterial blood pressure decreased by 43%, from 82 to 46 mmHg, during a mean hypotensive period of 32 min, without signs of tachyphylaxis. The arterial adenosine level increased from 0.15 ± 0.02 to 2.45 ± 0.65 μM (P < 0.01). Hypotension was caused by a profound decrease in peripheral vascular resistance (61 ± 3%, P < 0.01), which was accompanied by an increase in cardiac output (44 ± 9%, P < 0.01). Heart rate increased moderately by 16 ± 5% (P < 0.01). Pulmonary vascular resistance and central venous pressures were unaffected. Arterial lactate and PaO2 were unchanged, while whole body oxygen consumption was decreased by 13 ± 4% (P < 0.05). The AVDO2 across the brain was decreased by 37 ± 5% (P < 0.05) without signs of lactate formation. The authors conclude that adenosine rapidly induces a stable and easily controlled hypotension in humans by dilation of arterial resistance vasculature.

Nordic guidelines for neuraxial blocks in disturbed haemostasis from the Scandinavian Society of Anaesthesiology and Intensive Care Medicine.

Background: Central neuraxial blocks (CNBs) for surgery and analgesia are an important part of anaesthesia practice in the Nordic countries. More active thromboprophylaxis with potent antihaemostatic drugs has increased the risk of bleeding into the spinal canal. National guidelines for minimizing this risk in patients who benefit from such blocks vary in their recommendations for safe practice.

Clinical experience with adenosine for controlled hypotension during cerebral aneurysm surgery.

The cardiovascular effects of adenosine-induced hypotension were studied in 47 patients undergoing intracranial vascular surgery under neurolept anesthesia. Adenosine infusion (214 ± 18 μg · kg−1 min−1) decreased mean arterial pressure (MAP) by 42 ± 1% from 80 ± 1 to 46 ± 1 mm Hg for an average of 29 ± 5 min of hypotension. Hypotension was associated with a minor increase in heart rate (13 ± 2%) and with prolongation of the PR interval (9 ± 2%). ST-T depression did not occur except in one patient with a previous history of myocardial infarction. The adenosine-induced increase in cardiac index (42 ± 9%, n = 7) was associated with a 63 ± 10% decrease in systemic vascular resistance index (n = 7) while the pulmonary capillary wedge pressure remained unchanged. Adenosine metabolism was limited and there was no accumulation of the end metabolite, uric acid. Serum creatinine levels were normal in all patients postoperatively. We conclude that adenosine rapidly induces a stable and easily controlled hypotension in man without tachyphylaxis or rebound hypertension. There were no signs of renal or myocardial dysfunction except for dysrhythmias that occurred in two patients with a history of myocardial infarction.

Effects of propofol on cerebral blood flow, metabolism, and cerebral autoregulation in the anesthetized pig.

We studied the effects of propofol on the cerebral circulation and flow/pressure autoregulation in eight anesthetized pigs. Regional cerebral blood flow (rCBF) was measured with a cerebral venous outflow technique. Autoregulation was tested with angiotensin infusions and gradual blocks of the caval vein for hyper- and hypotensive challenges, respectively. Propofol was given in a bolus of 2.5 mg.kg-1 followed by an infusion starting at 12 mg.kg-1.h-1 and gradually reduced to 8 mg.kg-1.h-1. As expected, propofol caused a substantial reduction in cerebral metabolic rate of oxygen, which was accompanied by an increase in cerebrovascular resistance and a decrease in CBF. In the control situation, i.e., during background anesthesia (low-dose isoflurane+nitrous oxide) only, the autoregulation was well preserved, and its lower limit was found at a mean arterial blood pressure (MABP) of 48 mm Hg. Propofol did not affect autoregulation in the group as a whole: the slope of the regression line of regional cerebrovascular resistance (rCVR) versus MABP during blood pressure reduction (caval test) was not significantly changed during propofol when compared to the control, neither was the lower limit of autoregulation (MABP, 54 mm Hg). All pigs but one followed this response pattern. The nonautoregulating pig had a completely pressure-dependent rCBF during propofol anesthesia, despite a perfectly intact auto-regulation in the control situation. It is concluded that propofol in clinical dosage does not affect autoregulation in this pig model, although individual animals may display a different response pattern.

Central and Splanchnic Hemo dynamics in the Dog during Controlled Hypotension with Adenosine

Central and splanchnic hemodynamic effects during controlled hypotension induced by the administration of the endogenous vasodilator adenosine were studied in ten artificially ventilated dogs under neurolept anesthesia. Adenosine was administered as a continuous infusion in the aorta (n = 3), in the inferior vena cava (n = 3), and after pretreatment with dipyridamole (which inhibits the cellular uptake of adenosine) (n = 4) in a dose sufficient to maintain a mean arterial blood pressure (MABP) level of approximately 50 mmHg. Observations were made before and after 20 min of controlled hypotension. Basal arterial plasma levels of adenosine were in the 10−7 M range (&OV0398; = 0.4 μM). The hemodynamic response was similar in all three settings. Adenosine caused a profound decrease in systemic vascular resistance (SVR) (52%, P < 0.01) and preportal vascular resistance (PPR) (64%, P < 0.01), while hepatic arterial vascular resistance (HAR) increased by 49% (P < 0.05). Cardiac output increased (22%, P < 0.05) through increase of stroke volume (77%, P < 0.01), while heart rate decreased (28%, P < 0.01). Whole-body oxygen uptake decreased (14%, P < 0.01). Portal venous blood flow increased by 28% (P < 0.05), whereas hepatic arterial blood flow decreased by 70% (P < 0.01). In the preportal tissues, oxygen uptake decreased by 21% (P < 0.01). In contrast, hepatic oxygen consumption increased (53%, P < 0.05). Adenosine-induced hypotension was not associated with changes in plasma renin activity or the plasma concentration of norepinephrine. It is concluded that adenosine causes a rapidly induced and easily maintained hypotension and may be a potentially useful agent for controlled hypotension in patients.

Effect of Adenosine on Human Cerebral Blood Flow as Determined by Positron Emission Tomography

The effect of intravenous infusion of adenosine on CBF was studied in seven patients with cerebral arteriovenous malformation. The patients were examined with positron emission tomography with controlled ventilation using [15O] water and [11C] fluoromethane as tracers. Total and regional CBF were determined before and during infusion of adenosine at rates producing a reduction of the MABP by ∼10–40%. Six patients were normoventilated, and one was hyperventilated. Mean CBF in areas with normal brain tissue was 54 ml/100 g/min before adenosine infusion under normoventilation. Adenosine infusion increased mean CBF with 23–85%. Mean CVR was decreased with 43–65% and exceeded the percentage reduction of MABP in all normoventilated subjects. In the hyperventilated patient, the reduction of CVR was similar to the reduction of MABP, and CBF was unaffected, except for a 30% increase in the thalamus. It is concluded that intravenous administration of adenosine produces marked cerebral vasodilation in normoventilated subjects and that this response can be counteracted by hyperventilation.

Effects of adenosine-induced hypotension on myocardial hemodynamics and metabolism during cerebral aneurysm surgery.

The effects of adenosine-induced hypotension on central as well as myocardial hemodynamics and metabolism were studied in five neurolept-anesthetized patients without known heart or lung diseases, who were undergoing cerebral aneurysm surgery. Adenosine (217 ± 32 μg · kg−1 · mill−1) decreased mean arterial pressure 30% from 77 ± 5 to 54 ± 3 mm Hg. Cardiac filling pressures and heart rate remained unchanged during hypotension. Adenosine decreased systemic vascular resistance 50 ± 5% while cardiac index increased 39 ± 10%. Coronary sinus blood flow increased by 73 ± 13% from 128 ± 18 to 224 ± 36 ml/min with a concomitant decrease in calculated coronary vascular resistance (66 ± 4%). Both systemic and myocardial arteriovenous oxygen content differences decreased, and myocardial oxygen consumption decreased 42 ± 9%. There were no alterations in myocardial fractional lactate extraction. Arterial plasma renin activity and arterial catecholamine levels were unaffected by hypotension. It is concluded that adenosine hypotension in this group of patients produced a hyperkinetic circulation in the systemic as well as in the myocardial vascular bed. Cardiac output and coronary sinus blood flow increased at the same time as myocardial oxygen consumption decreased.

Cerebral blood flow and metabolism during adenosine–induced hypotension in patients undergoing cerebral aneurysm surgery

The effects of adenosine–induced hypotension on cerebral blood flow (CBF), cerebral metabolic rate of oxygen (CMRo2), and cerebral lactate production, together with systemic haemodynamics, were studied in 10 patients undergoing cerebral aneurysm surgery in neurolept anaesthesia with controlled hyperventilation. CBF changes were determined in six of the patients with a retrograde thermodilution technique in the jugular vein. Hypotension was induced with a continuous infusion of adenosine in the superior vena cava. The dose range was 0.06–0.35 mg/kg/min, and this caused a 42% reduction in mean arterial blood pressure (MABP) from 79 × 4 to 46 × 1 raraHg (10.5 × 0.5 to 6.1 × 0.1 kPa) through a profound reduction in systemic vascular resistance (SVR), which amounted to 61%. No significant change occurred in CBF. Whole body AV–difference of oxygen was decreased by 37%, and cerebral AV–difference by 28%, corresponding to reductions in whole body oxygen uptake and CMR02 of 16 and 17%, respectively. Cerebral AV–difference of lactate did not change. In the posthypotensive period MABP was increased by 10%, together with a minor increase in CBF (15%). It is concluded, that adenosine–induced hypotension at MABP levels between 40–50 mmHg (5.3–6.7 kPa) does not affect cerebral oxygenation unfavourably, and may even offer a protective effect by reducing cerebral oxygen demand. The slight CBF increase in the posthypotensive period was probably secondary to an increase in MABP together with a blunted autoregulation, but in no case was this effect considered to be harmful for the patient.

Renin Release during Controlled Hypotension with Sodium Nitroprusside, Nitroglycerin and Adenosine: A Comparative Study in the Dog

The haemodynamic effects of i. v. infusions of sodium nitroprusside (SNP), nitroglycerin (TNG), and adenosine were studied in dogs in parallel with quantitative determinations of plasma renin activity (PRA) by radioimmunoassay. The drugs were given for controlled hypotension, and the mean arterial blood pressure (MABP) was decreased to approximately 50 mmHg (6.7 kPa). Arterial blood samples for PRA were collected at 10‐min intervals. During the last interval the dogs were subjected to haemorrhagic shock. SNP‐induced hypotension could be maintained only with a stepwise increase in infusion rate, from 11.8 to 16.0 μg ⋅ kg‐1 ⋅ min‐1 (P<0.05). TNG could not produce the desired blood pressure level, but gradually increasing doses induced a gradually decreasing MABP (80‐60 mmHg) (10.7–8.0 kPa). During adenosine‐induced hypotension, a perfectly stable blood pressure level was maintained without dose adjustments. Both SNP and TNG induced blood pressure‐dependent increases in PRA, while no changes in PRA were seen during adenosine‐induced hypotension. Nor could haemorrhagic shock, which induced further increases in PRA during SNP‐ and TNG‐induced hypotension, alter PRA during adenosine infusions. We conclude that adenosine differs markedly from conventional hypotensive drugs such as SNP and TNG with respect to stability of action and dose requirements, and that this stability is related to an inhibited increase in renin release.

Sodium Nitroprusside as a Hypotensive Agent in Intracranial Aneurysm Surgery

Sodium nitroprusside (SNP) was used to induce hypotension during intracranial aneurysm surgery in 67 patients. The effects of SNP infusion (0.1 mg/ml) on blood pressure were rapid and it was easy to adjust blood pressure to desired levels in most patients. When SNP was stopped, the blood pressure returned instantly to the initial level. In eight patients an increase to about 25% or more above prehypotensive level was seen, counteracted in two patients by administration of small doses of halothane. There was a mean increase of 36% in heart rate. Total doses of SNP were 0.05–120 mg (mean: 10.8), corresponding to 0.08–6.8 μg/kg/min (mean: 1.9). No metabolic acidosis indicating cyanide intoxication was observed. Tachyphylaxis was seen in three patients, and SNP had to be discontinued in one. It is concluded that SNP gives a rapid and effective hypotension but tachyphylaxis and subsequent danger of cyanide intoxication exist. Therefore, in some cases SNP has to be replaced by or combined with some other hypotensive agent to achieve the desired effect. As there is a risk of impairment of cerebral autoregulation after the use of SNP, it is important to avoid sudden and prolonged blood pressure fluctuations, and to continue with controlled hyperventilation in the postoperative period to reduce the risk of brain oedema and high intracranial pressure.