Title: Paradoxal effect of atropine: are we doing our best to prevent it?

Author(s): Alves DR, Amim S, Gonçalves N

Institute(s):Centro Hospitalar de Lisboa Ocidental, Dept of Anaesthesiology, Lisboa, Portugal

Text:
Background and Goal of Study: Atropine was isolated over 180 years ago, but some peculiarities of its action are still surrounded in doubt. Small doses of the drug have been found to cause a paradoxal effect, and in adults international resuscitation guidelines uphold the use of 0,5mg as an initial dose, independent of body weight. However, different clinicians prefer to use 10 mcg/Kg. We decided to see if there was any difference in the incidence of paradoxal effects of atropine with either option, auditing local practice in the last year.
Materials and methods: Retrospective study (audit) comparing data from patients treated with 0,5mg or 10mcg/Kg after developing severe intraoperative bradicardia (< 40 bpm) accompanied by a drop in blood pressure.
Results and discussion: In 12 months we identified 12 patients treated with 0,5mg atropine, 5 of which (41,7%) developed paradoxal effect of atropine, with development of a junctional rhythm that promptly reverted after administration of a further dose of 0,5mg atropine. Most of those who did develop paradoxal effect were receiving remifentanyl (5 out of 7), whereas this opioid was only used in 1 of the 5 patients treated with 0,5mg atropine that did not develop paradoxal effect.
On the other hand, during the same time period 4 patients were treated with 10 mcg/Kg of atropine, none of which developed paradoxal effect, even though 3 of them were receiving remifentanyl.
The number of patients involved does not allow for statistically significant changes between groups to be identified either through Fisher's exact test or Mann-Whitney test. However, logistic regression with the outcome variable defined as paradoxal effect development and independent variables being atropine dose and remifentanyl use leads to a statistically significant model (Omnibus test p- value=0,012), statistically adjusted to the data (Hosmer-Lemeshow test p-value=1,0), with a Nagelkerke pseudo-R2 of 0,571, even though individual Wald statistics show a p-value>0,05. Still, the small n advises caution in this analysis.
Conclusions: The present study shows that paradoxal effect of atropine is clinically more common than usually considered, occurring in day-to-day practice. However, the number of patients studied was too small to draw any firm conclusions. While a small dose of atropine (0,5mg independently of body weight) and possibly remifentanyl use appear to constitute risk factors, further, larger studies are needed to clarify the matter.