LAUSR

We thank the authors for the report on compartment syndrome in the hand of a patient following phenylephrine infusion.1 There are several aspects of the case that we believe require careful consideration before concluding that phenylephrine was the cause of compartment syndrome. First, the patient had a very large volume (9 L) of crystalloid resuscitation. Combined with term pregnancy fluid retention, the limited time (20-60 minutes) for which crystalloids remain intravascular,2 and permeable capillaries given the patient’s inflammatory milieu, the extravascular and interstitial tissue compartments most certainly would have been voluminous. Moreover, venous thrombosis (noted at fasciotomy) is not unexpected given the hypercoaguable risks posed by pregnancy, two surgical procedures in a short time frame, and critical health state. Second, the intravenous (IV) catheter is tethered to the skin. As the interstitial and subcutaneous spaces of the hand swell for the aforementioned reasons, this distracts the venous catheter tip further away from the vein’s lumen, increasing the likelihood of IV catheter migration outside of the vessel. In a reference used by the authors, the hand is identified as an insertion site to avoid a given the potential for IV catheter dislodgement.3 Taken together, it is very plausible that the IV catheter may have been passively “pulled” out of the vein by expanding subcutaneous tissues of the hand at some point during the substantial fluid resuscitation, subsequent emergency laparotomy, and critical care sequence. Indeed, at the time of fasciotomy, hand muscles were noted to be “tense and edematous” with “significant fluid in the subcutaneous tissues.”1 Theses findings are more in keeping with a dislodged IV catheter through which fluids were subcutaneously administered than vasoconstrictor-mediated injury. Third, vasopressors are often administered via infusion pumps. Alarms on infusion pumps are recognized to be insufficient to detect a dislodged IV catheter and contribute to compartment syndrome presentations.4 It is unclear from the report if IV fluid pumps were used. Fourth, the authors correctly identify no previous cases of compartment syndrome involving phenylephrine. Two references cited by the authors note no sequelae from peripheral IV phenylephrine infusions that became interstitial.3,5 Moreover, at least 1 manufacturer’s monograph lists the subcutaneous route as permissible for phenylephrine administration.6 The fact that several patients without a history of massive fluid resuscitation (in the studies cited by the authors)3,5 developed displaced IV catheters resulting in interstitial administration of phenylephrine without sequelae further casts doubt on phenylephrine as a sole cause of edema-related compartment syndrome. Fifth, drug exposures require particular consideration. It is unclear from the manuscript how much phenylephrine (rate, concentration, dose, and duration of phenylephrine infusion) was administered. Additionally, hypovolemic shock requiring blood transfusion is often managed with IV calcium to augment coagulation. Calcium chloride and gluconate, due to hyperosmolarity, are both recognized as medications associated with extravasation injury and potential for calcium-mediated vasoconstriction injury.7 It is unclear if calcium was administered through the IV. Association does not equal causation. Based on the issues above, we implore the authors for further information to properly support their bold claim of phenylephrine as the causative agent of compartment syndrome.