Hypotension and status epilepticus in relation to intrathecal morphine administration
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
Serum Pentraxin-3 levels in acute cholecystitis: Helpful in emergency decision- making? referencing MS 21243.
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
Correspondence / American Journal of Emergency Medicine 38 (2020) 1679-1694 1683
E-mail address: [email protected].
Guy L. Weinberg
University of Illinois at Chicago College of Medicine, Jesse Brown Veterans
Administration Medical Center, Chicago, IL, USA
?Corresponding author.
E-mail address: [email protected].
27 February 2020
https://doi.org/10.1016/j.ajem.2020.03.065
References
- Sidlak AM, Yanta JH, Lynch MJ. Intrathecal bupivacaine and morphine toxicity leading to transient hypotension and delayed status epilepticus. Am J Emerg Med 2020;38 (8):1683.
- Lutfy K, Woodward RM, Keana JF, Weber E. Inhibition of clonic seizure-like excitatory effects induced by intrathecal morphine using two NMDA receptor antagonists: MK- 801 and ACEA-1011. Eur J Pharmacol 1994;252:261-6.
- Yoburn BC, Lutfy K, Sierra V, Tortella FC. Tolerance develops to spinal morphine analgesia but not morphine-induced convulsions. Eur J Pharmacol 1990;176: 63-7.
- Kronenberg MF, Laimer I, Rifici C, Saltuari L, Bramanti P, Moriggl U, et al. Epileptic sei- zure associated with intracerebroventricular and intrathecal morphine bolus. Pain 1998;75:383-7.
- Sauter K, Kaufman HH, Bloomfield SM, Cline S, Banks D. Treatment of high-dose intra- thecal morphine overdose. Case report. J Neurosurg 1994;81:143-6.
- Yilmaz A, Sogut A, Kilinc M, Sogut AG. Successful treatment of intrathecal morphine overdose. Neurol India 2003;51:410-1.
- Fettiplace MR, Weinberg G. The mechanisms underlying Lipid resuscitation therapy. Reg Anesth Pain Med 2018;43:138-49.
Intrathecal bupivacaine and morphine toxicity leading to transient hypotension and delayed status epilepticus
We appreciate the thoughtful and constructive feedback sub- mitted. We certainly acknowledge the potential contribution of morphine to the clinical presentation of our patient [1-4], but the responsibility of any one drug to the presentation is largely un- knowable without data on the toxicity of intrathecal bupivacaine. Excessive CNS delivery of each drug could logically be anticipated to cause deleterious effects. It would be overly dismissive to ex- clude bupivacaine’s potential contribution. First, bupivacaine was administered in an overdose of equal proportion relative to its therapeutic spinal dose as morphine. Second, there are no prior re- ports of intrathecal bupivacaine administration at a similar dose as observed in our case. Additionally, direct neuronal toxicity from bupivacaine and/or other local anesthetics has previously been de- scribed [5]. Finally, though cases of intrathecal morphine toxicity are present in the literature, they are rare and limited by confound- ing factors with the dose of morphine in our case being lower than previous cases (100 mg vs 250-510 mg) [2-4]. In one case, a patient was found to have an intracranial hemorrhage [3]. In all three re- ports, high doses of naloxone were administered which two au- thors felt could have led to precipitated withdrawal contributing to the clinical picture [3,4]. Cessation of Naloxone therapy in the latter case led to resolution of Severe hypertension [4]. Thus, con- tinued or higher dosing of naloxone may not be warranted and po- tentially counterproductive. In fact, more aggressive therapies were performed in these case reports such as CSF irrigation and drainage, and intravenous barbiturate infusions [2-4]. In our case of severe toxicity, the response to therapy and relatively abbrevi- ated course may have indicated a potential benefit of intravenous fat emulsion (IFE). Ultimately, the “clinical pearls” that we drew from our experience are 1) Cardiotoxicity after an intrathecal bupivacaine overdose was limited, and 2) While antidotal thera- pies have been suggested in case reports following intrathecal
drug delivery overdose, standard aggressive critical care of status epilepticus should not be delayed or subverted by reliance on those hypothesized, but largely unstudiED treatments.
Alexander M. Sidlak, MD* Joseph H. Yanta, MD
Division of Medical Toxicology, Department of Emergency Medicine, University of Pittsburgh School of Medicine, USA
*Corresponding author at: Division of Medical Toxicology, Department of Emergency Medicine, University of Pittsburgh School of Medicine, USA.
E-mail address: [email protected].
Michael J. Lynch MD
Pittsburgh Poison Center, Pittsburgh, PA, USA
31 March 2020
https://doi.org/10.1016/j.ajem.2020.03.064
References
Yoburn BC, Lufty K, Sierra V, Tortella FC. Tolerance develops to spinal morphine anal- gesia but not morphine-induced convulsions. Eur J Pharmacol 1990;176:63-7.
- Ylimaz A, Sogut A, Kilinc M, Sogut AG. Succesful treatment of intrathecal morphine overdose. Neurol India 2003;51:410-1.
- Sauter K, Kaufman HH, Bloomfield A, et al. Treatment of high-dose intrathecal mor- phine overdose: care report. J Neurosurg 1994;81(1):143-6.
- Groudine SB, Cresanti-Daknis C, Lumb PD. Successful treatment of a massive intrathe- cal morphine overdose. Anesthesiology 1995;82(1):292-5.
- Verlinde M, Hollmann MW, Stevens MF, et al. Local anesthetic-induced neurotoxicity. Int J Mol Sci 2016;17(2):339.
Flow-safe disposable CPAP efficiency in cardiogenic pulmonary oedema
To Editor,
We have read with great interest the study “Is flow-safe disposable continuous positive airway pressure (CPAP) system as effective as non- invasive mechanical ventilation (NIMV) in the treatment of acute cardio- genic pulmonary oedema”, performed by Ilhan et al. and published on American Journal of Emergency Medicine [1], where two treatment op- tions in patients with cardiac pulmonary edema in an emergency depart- ment are compared. We congratulate the authors for this original contribution. The authors consider that both options have a solid basis of application in patients with cardiogenic pulmonary edema. However, we consider that there are some points to consider for an adequate eval- uation of the results:
Flow-safe CPAP settings. We consider that the authors should pro- vide a more detailed description of flow-safe CPAP methodology, namely on titration.
- Duration treatments: we consider that the authors base the use of slow-safe CPAP system in emergency department. However, the treatment time compared to the NIMV are not well clarified nor are the emergency department length stay in both groups.
- Discrepancy on COPD prevalence: as the authors remarked in dis- cussion section, COPD prevalence was significantly higher on NIMV group. This is a factor of major concern regarding the efficacy of flow-safe CPAP, since COPD is a common comorbidity in acute car- diogenic pulmonary oedema, both conditions promoting each other aggravation. Also, there is a significant different on presence of initial hypercapnia, with NIMV being used preferably on hypercapnic patients.