We agree with Dr. Mandal that the pathogenesis of negative-pressure pulmonary edema is likely multifactorial and that the most obvious cases are associated with sustained negative pulmonary pressure, e.g. , during laryngospasm. However, there is increasing evidence that the initiating cause of negative-pressure pulmonary edema can be a relatively subtle airway obstruction that might be unnoticed until unexplained pulmonary edema develops. 1
We also agree that an acute impairment of left ventricular function was likely present, and this probably contributed to the development of edema. This impairment is considered part of the pathogenesis of negative-pressure pulmonary edema and is secondary to a significantly increased left ventricular afterload caused by increased negative intrathoracic pressure with a closed airway, i.e. , in our case, during hiccups. The intraoperative echocardiogram that was obtained to rule out ongoing cardiac dysfunction only showed residual mild abnormalities consistent with right ventricular afterload increase. The full report that was provided in the original manuscript but shortened for editorial reasons was:“Mild mitral valve prolapse with mild mitral regurgitation. Normal aorta. Good left ventricular function with shortening fraction of 33%. Trivial pulmonary insufficiency with gradient of 13 mmHg predicting mild pulmonary hypertension. Good right ventricular function with no tricuspid regurgitation.” Even after review, the cardiologist believed that this was inconsistent with a primary cardiogenic cause for the edema.
Dr. Mandal suggests that laryngoscopy and endotracheal intubation might have caused sufficient arterial hypertension to cause cardiogenic edema. This would imply either a very light level of anesthesia during intubation or the initiation of a neurogenic edema. We believe neither was the case. The halothane induction lasted more than 10 min, and the end-tidal halothane concentration (1.2–1.3%) was sufficient to cause no response to several cannulation attempts just 60 s before paralysis and intubation, which makes inadequate anesthesia unlikely. Secondly, neurogenic edema, as discussed in the case report, is not a transient, short-lasting phenomenon.
Lastly, Dr. Mandal mentions that hiccups could have been elicited via stimulation of the epipharynx by the patient’s copious salivation. 2This reference and the related discussion were also removed in the review process of the original manuscript. We, too, believe that saliva might have had a hiccup-triggering effect in the partially anesthetized patient. Indeed, when this patient presented months later for her canceled dental procedure, she again was administered oral midazolam for premedication, and it was planned to insert an intravenous cannula during nitrous oxide sedation. Within 30 s of nitrous oxide administration, vigorous hiccups developed. The patient rapidly was induced intravenously, and the rest of the anesthetic procedure was uneventful.
Finally, we agree that an anticholinergic premedication administered early enough and in sufficient amount might help to prevent this triggering by decreasing oral secretions.