1682 Correspondence / American Journal of Emergency Medicine 38 (2020) 1679-1694

The authors respond: Sensitivity and specificity in serum testing for acute cholecystitis

We read the issues that the authors stated for our manuscript [1] and thank their interest.

The sensitivity of a test is to correctly predict those patients with the disease theoretically. But, it can be described in variety of ways, typically such as sensitivity being the ability of a screening test to detect a true positive, being based on the true positive rate, reflecting a test’s ability to correctly identify all people who have a condition, or, if 100%, identi- fying all people with a condition of interest by those people testing pos- itive on the test [2,3].

The specificity of a test is to correctly predict those patients without the disease theoretically. But, it test is defined in a variety of ways, typ- ically such as specificity being the ability of a screening test to detect a true negative, being based on the true negative rate, correctly identify- ing people who do not have a condition, or, if 100%, identifying all pa- tients who do not have the condition of interest by those people testing negative on the test. Selecting the optimal balance of sensitivity and specificity depends on the purpose for which the test is used [2,3]. In general, a screening test should be highly 100% or almost 100% sensi- tive, whereas a follow-up confirmatory test should be highly 100% or al- most 100% specific [2]. We found that serum Pentraxin 3 levels of >= 4.9 ng/mL could predict GP with a sensitivity of 75% and a specificity of 85% and serum pro-ADM levels of >= 97 nmol/L with sensitivity and specificity of 100% and 95% [4]. As you have noted, this values may change if the number of cases increases statistically. We have already stated that the relatively low number of evaluated cases is a limitation it is necessary to undertake a further study with a higher number of cases to obtain more reliable results [4].

You state that the lack of control for confounders like diabetes com- plicates the interpretation of the study results. We think about it like you and we have mentioned in the limitation section that an important issue in the study is the lack of comparison between healthy individuals and acute cholecystitis cases and such a comparison may provide a bet- ter understanding of the relationship between the investigated markers and acute cholecystitis with gallbladder perforation [4].

A. Algin

Department of Emergency Medicine, Umraniye Training and Research

Hospital, Istanbul, Turkey

U. Gulacti

Department of Emergency Medicine, Adiyaman University Training and

Research Hospital, Adiyaman, Turkey

?Corresponding author at: Adiyaman Egitim Ve Arastirma Hastanesi Acil

Servis, Adiyaman, Turkey.

E-mail address: [email protected].

I. Inan

Department of Radiology, Adiyaman Training and Research Hospital,

Adiyaman, Turkey

M.O. Erdogan

Department of Emergency Medicine, Bahcesehir University Medical

Faculty, Istanbul, Turkey

S. Colak Department of Emergency Medicine, Saglik bilimleri University Haydarpasa Numune Training and Research Hospital, Istanbul, Turkey

M. Sariaydin

Department of Internal Medicine, Adiyaman Training and Research

Hospital, Turkey

1 October 2019

https://doi.org/10.1016/j.ajem.2019.158502

References

1. Serum Pentraxin-3 levels in acute cholecystitis: Helpful in emergency decision- making? referencing MS 21243.
2. Trevethan R. Sensitivity, specificity, and predictive values: foundations, pliabilities, and pitfalls in research and practice. Front Public Health 2017;5:307. https://doi. org/10.3389/fpubh.2017.00307.
3. Lalkhen AG, McCluskey A. Clinical tests: sensitivity and specificity. Contin Educ Anaesthesia Crit Care Pain 2008;8(6):221-3. https://doi.org/10.1093/bjaceaccp/ mkn041.
4. Algin A, Gulacti U, Inan I, Erdogan MO, Colak S. Sariaydin M relationship between serum Pentraxin 3 and pro-adrenomedullin levels with acute cholecystitis. Am J Emerg Med 2019;37(7):1268-72. https://doi.org/10.1016/j.ajem.2018.09.024 Epub 2018 Sep 15.

Hypotension and status epilepticus in relation to intrathecal morphine administration

Editor – We were very interested to read the recent case report by Sidlak et al. [1] describing signs of central nervous system (CNS) toxicity following intrathecal pump refill with morphine and bupivacaine. The patient developed “sensory neuropathy” and flaccid paralysis of the lower extremities, hypotension, al- tered mental status and status epilepticus. The authors ascribed most of these symptoms to bupivacaine “neurotoxicity” and the failure of lipid emulsion infusion to resolve the seizures to “poor CNS penetration”. We applaud the authors’ concern for and con- sideration of Local anesthetic toxicity since early diagnosis and treatment of this Life-threatening complication can save lives. However, we disagree with the authors’ diagnosis of bupivacaine-induced “neurotoxicity” given that both the sensori-motor loss and hypotension are entirely consistent with simple Spinal anesthesia and that the status epilepticus is ex- plained completely by morphine central neurotoxicity. The latter is described both in animal models [2,3] and in several published case reports [4-6] of persistent seizures following intrathecal morphine administration. In these cases, the seizures appeared to respond to high dose Naloxone administration. This diagnosis also explains why lipid emulsion infusion did not have an effect; the seizures simply were not related to bupivacaine. Lipid infu- sion can accelerate resolution of CNS signs of systemic local anes- thetic toxicity – primarily by a pharmacokinetic effect [7] that does not rely on “CNS penetration”; however, it is expected to be ineffective in reducing brain morphine levels based on the low log P for this opiate. In sum, it is wise to consider systemic local anesthetic toxicity in any patient experiencing altered men- tal or cardiovascular status in the setting of regional anesthesia. It is equally important to add other possibilities to the differential diagnosis, especially when the patient’s response to treatment does not comport with expectations.

Financial support

This is a non-funded work.

Declaration of competing interest

Dr. Weinberg is an officer and shareholder of ResQ Pharma, Inc.

Bruno Megarbane Department of Medical and Toxicological Critical Care, Lariboisiere Hospital, Paris University, INSERM UMRS-1144, University, Paris, France