Dose-response study of dapiprazole HCl in the reversal of mydriasis induced by 2.5% phenylephrine.

Dapiprazole HCL is currently available in the United States for reversal of diagnostic mydriasis. The recommended dosage for this indication is 2 drops followed 5 minutes later by 2 drops. We studied the dose-response profile and tolerance of three different treatment regimens: 1 drop alone, 1 drop followed by 1 additional drop 5 minutes later, and 2 drops followed by 2 additional drops 5 minutes later. Sixty normal male and female volunteers between 18 and 40 years of age were recruited for a double-masked, placebo-controlled, crossover study in which each eye of each subject was dilated with 2.5% phenylephrine. After one hour, one eye was treated with 0.5% dapiprazole, and the contralateral eye was treated with placebo. Each subject was treated with each of the three dapiprazole regimens in three different study sessions separated by at least 5 days (drug half-life in the eye is 5 hours). Analysis of AUC demonstrated no significant difference (P = 0.620) between the 1 drop regimen and the 2 + 2 regimen. A single drop of dapiprazole has a clinical effect equivalent to the 2 + 2 drop regimen in eyes dilated with 2.5% phenylephrine, which should improve the cost-effectiveness of this mydriolytic agent.

External cardiac compression may be harmful in some scenarios of pulseless electrical activity.

Pulseless electrical activity occurs when organised or semi-organised electrical activity of the heart persists but the product of systemic vascular resistance and the increase in systemic arterial flow generated by the ejection of the left venticular stroke volume is not sufficient to produce a clinically detectable pulse. Pulseless electrical activity encompasses a very heterogeneous variety of severe circulatory shock states ranging in severity from pseudo-cardiac arrest to effective cardiac arrest. Outcomes of cardiopulmonary resuscitation for pulseless electrical activity are generally poor. Impairment of cardiac filling is the limiting factor to cardiac output in many scenarios of pulseless electrical activity, including extreme vasodilatory shock states. There is no evidence that external cardiac compression can increase cardiac output when impaired cardiac filling is the limiting factor to cardiac output. If impaired cardiac filling is the limiting factor to cardiac output and the heart is effectively ejecting all the blood returning to it, then external cardiac compression can only increase cardiac output if it increases venous return and cardiac filling. Repeated cardiac compression asynchronous with the patient's cardiac cycle and raised mean intrathoracic pressure due to chest compression can be expected to reduce rather than to increase cardiac filling and therefore to reduce rather than to increase cardiac output in such circumstances. The hypothesis is proposed that the performance of external cardiac compression will have zero or negative effect on cardiac output in pulseless electrical activity when impaired cardiac filling is the limiting factor to cardiac output. External cardiac compression may be both directly and indirectly harmful to significant sub-groups of patients with pulseless electrical activity. We have neither evidence nor theory to provide comfort that external cardiac compression is not harmful in many scenarios of pulseless electrical activity. Investigation using a variety of animal models of pulseless electrical activity produced by different shock-inducing mechanisms is required to provide an evidence base for resuscitation guidelines.

Selectatec switch malfunction.

Malfunction of a Selectatec switch mechanism is reported which resulted in complete cessation of gas flow to the patient system. Anaesthetists are alerted to this potential hazard.

Kinin-mediated anaphylactoid reaction implicated in acute intra-operative pulseless electrical activity.

A 65-year-old patient undergoing total hip replacement under general anaesthesia suffered acute pulseless electrical activity with a fatal outcome. A kinin-mediated analphylactoid reaction following administration of a polygeline plasma expander (Haemaccel) was implicated by in vitro testing. This case report illustrates the diagnostic difficulties posed by non-histaminoid anaphylactoid reactions and the resistance to epinephrine of kinin-mediated hypotension.