Epinephrine plasma metabolic clearance rates and physiologic thresholds for metabolic and hemodynamic actions in man.

Clutter, William E.; Bier, Dennis M.; Shah, Suresh D.; Cryer, Philip E.

doi:10.1172/jci109840

Cited by 560 publications

(236 citation statements)

References 32 publications

(29 reference statements)

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“…The thresholds for the other effects of epinephrine (such as changes in heart rate, glucose, alanine, or growth hormone) are variable, ranging from twice to ten times the basal levels. 23 Our observations suggest that further controlled studies are warranted to examine the predictive value and dose-related threshold for T-wave changes.…”

Section: Discussionmentioning

confidence: 80%

Detection of intravascular injection of regional anaesthetics in children

1997

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Purpose: Detection of intravascular injection of local anaesthetic during placement of regional blocks in children by using epinephrine-induced tachycardia or hypertension may produce false positive and false negative findings. This study evaluates ECG changes as markers of intravascular injection of local anaesthetics with epinephrine, during placement of epidural blocks in children. Methods: Observational study in a teaching hospitaJ of all epiduraJ anaesthetics administered to paediatric patients during one year, General anaesthesia, where used, was not controlled. An ECG rhythm strip was recorded during test dose iniection and analyzed for changes in rate, rhythm, and T-wave configuration. Results: During the study period, 742 paediatric epidural blocks were administered. There were 644 caudal (284 without catheters), 97 lumbar, and one thoracic epidural anaesthetics. Satisfactory placement was achieved in 97.7% of patients. Intravascular injection was detected in 42 (5.6%) of epidural anaesthetics (3.8% and 6.7% of straight needle and catheter injections, respectively). Detection was by immediate aspiration of blood in six patients, and by heart t-ate increases >10 bpm in 30. Five had heart rate decreases suggesting a baroreceptor response. Five had heart rate increases < I 0 bpm that were possible responses to noxious stimuli. Of 30 patients with known intravascular injection and for whom ECG strips were available, 25 (83%) had T-wave amplitude ~ncreases > 25%, and 29 (97%) had ECG changes in T-wave or rhythm in response to the epinephrine injection. There were no false positives. Conclusion: In order to reduce risks associated with epidural anaesthesia in children, epinephrine should be added to the local anaesthetic test dose, the ECG should be monitored continuously for changes in heart rate, rhythm, and T-wave amplitude. Epidural injections should be given in small increments.

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Section: Discussionmentioning

confidence: 80%

Detection of intravascular injection of regional anaesthetics in children

1997

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“…Similarly the increase in both growth hormone and cortisol may have r-adrenoceptor blockade and hypoglycaemia been due to the effect of increased levels of circulating catecholamines on secretion of these hormones (Blackard & Hubbel, 1970;Taylor & Fishman, 1988). Direct adrenergic stimulation of glucagon secretion has been reported by some (Gerich et al, 1976), but not all groups (Clutter et al, 1980), and one might have expected ,-adrenoceptor blockers to reduce glucagon release although this would be offset to some extent by the greater plasma adrenaline concentration.…”

Section: Resultsmentioning

confidence: 95%

Beta‐adrenoceptor blockade and hypoglycaemia. A randomised, double‐ blind, placebo controlled comparison of metoprolol CR, atenolol and propranolol LA in normal subjects.

Kerr¹,

Macdonald²,

Heller³

et al. 1990

Brit J Clinical Pharma

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1. The effect of 1 week of treatment with propranolol LA (160 mg), atenolol (100 mg) and metoprolol CR (100 mg) on awareness of and the physiological responses to moderate hypoglycaemia were compared with placebo using a randomised, cross‐over design in 12 healthy volunteers. 2. All three beta‐adrenoceptor antagonists reduced resting heart rate, systolic blood pressure and heart rate responses to submaximal exercise compared with placebo. 3. Under hyperinsulinaemic (60 mu m‐2 min‐1) clamp conditions, at a blood glucose of 2.5 mmol l‐1, atenolol prevented the rise in systolic and atenolol and metoprolol CR prevented the fall in diastolic blood pressure usually associated with hypoglycaemia. At this level of hypoglycaemia, the expected increase in heart rate was inhibited by atenolol but not metoprolol CR. Pre‐ treatment with propranolol LA resulted in a significant pressor response and a bradycardia during hypoglycaemia. In addition the normal increase in finger tremor was abolished by propranolol LA. 4. During hypoglycaemia all three beta‐adrenoceptor blockers augmented sweating compared with placebo but hypoglycaemic symptoms, awareness and slowing of reaction time were the same with drugs and placebo. 5. The rise in plasma adrenaline and other counter‐regulatory hormones during hypoglycaemia was enhanced by beta‐adrenoceptor blockade. 6. We conclude that beta‐adrenoceptor antagonists modify the physiological and hormonal responses to, but do not adversely affect awareness of, moderate hypoglycaemia in healthy volunteers.

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“…22,23 During hormone infusions, the plasma threshold concentration for cardiovascular and metabolic changes is about 10 times lower for adrenaline than for noradrenaline. 10,22 Thus, it is impossible to mimic physiological events completely by noradrenaline infusions, and for these reasons adrenaline was chosen for the present study. The threshold for metabolic effects observed during adrenaline infusion in this experiment was well below the concentrations observed during ordinary activities like standing or mild exercise.…”

Section: Discussionmentioning

confidence: 99%

The effect of sibutramine on resting energy expenditure and adrenaline-induced thermogenesis in obese females

1999

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BACKGROUND: Sibutramine, an inhibitor of serotonin and noradrenaline uptake, reduces appetite to cause weight loss. This study tested the hypothesis that an increase in energy expenditure also contributes to this weight loss. In addition, the effects of sibutramine on adrenaline induced changes in heart rate and cardiac output were determined METHODS: Nineteen obese females randomly received either sibutramine 15 mg daily or placebo for 12 weeks along with dietary advice. Resting energy expenditure (REE) was measured and then energy expenditure was measured during a 30 min infusion of adrenaline (25 ngaminakg IBW). Cardiac output and heart rate, measured by Duplex Colour Doppler ultrasonography, were similarly measured in the basal state and post adrenaline. All measurements were recorded at baseline and then after 12 weeks. RESULTS: Ten patients who received sibutramine reduced their weight by 8.1 AE 3.8% while 9 placebo treated subjects reduced their weight by 5.1 AE 4.4%, P 0.13. In absolute terms, REE decreased in placebo subjects from 1500 AE 201 kcala24 h to 1357 AE 231 kcala24 h (9.4 AE 9.9%) and in sibutramine subjects from 1540 AE 184 kcala24 h to 1444 AE 128 kcala24 h (5.3 AE 12.0%), P 0.77. The increased weight loss in the sibutramine group was associated with an increase in the FFM adjusted REE (2.2 AE 16.1%) unlike the expected decrease (5.8 AE 9.5%) in the placebo group (P 0.11). There was some suggestion (P 0.09) that the usual positive correlation between loss of weight and decline in REE was lost in the sibutramine group (r 7 0.30) compared with placebo (r 0.35). There was a negative correlation between loss of FFM and decline in REEakg FFM and (P 0.029) which was not evident in placebo (P 0.83). Adrenaline induced energy expenditure was similar in the two groups at the end of the 12 week period and there were no signi®cant cardiovascular changes between the two groups. CONCLUSIONS: Sibutramine limits the decline in REE associated with weight loss, equivalent to about 100 kcalad. This could allow greater numbers of people to maintain a greater degree of weight loss.

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Epinephrine plasma metabolic clearance rates and physiologic thresholds for metabolic and hemodynamic actions in man.

Cited by 560 publications

References 32 publications

Detection of intravascular injection of regional anaesthetics in children

Detection of intravascular injection of regional anaesthetics in children

Beta‐adrenoceptor blockade and hypoglycaemia. A randomised, double‐ blind, placebo controlled comparison of metoprolol CR, atenolol and propranolol LA in normal subjects.

The effect of sibutramine on resting energy expenditure and adrenaline-induced thermogenesis in obese females

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