Case report

A six-year-old male patient weighing twenty-five kilograms was consulted at the paediatric cardiology department due to bradycardia detected during hospitalisation in the paediatric haematology ward. At presentation, he had no active complaints. His medical history revealed that he had been receiving prophylactic treatments due to a diagnosis of common variable immunodeficiency (NFKB2 deficiency) and was undergoing chemotherapy for non-Hodgkin lymphoma. On physical examination, he appeared pale, and hepatosplenomegaly was present. Heart sounds were distant and arrhythmic. Blood pressure was 90/40 mmHg, and heart rate was 39 beats per minute. Electrocardiography at admission demonstrated second-degree Mobitz type I atrioventricular block (Figure 1). Echocardiography revealed minimal aortic regurgitation and minimal pericardial effusion surrounding the heart. Upon further history taking, it was learned that transdermal fentanyl therapy (0.5 micrograms/kilograms) had been initiated two days earlier for chronic pain. It was not the time for active chemotherapy, and no additional sedative agent was being used. Consequently, it was recommended to discontinue transdermal fentanyl therapy, monitor the patient, and place a 24-hour Holter monitor while taking precautions for emergencies. Laboratory tests were performed to exclude myocarditis; troponin and CK-MB levels were negative.

Figure 1.

Second-degree Mobitz type 1–type 2 AV block seen on ECG at admission.

Figure 1. Long description

Panel A: A line graph showing the electrical activity of the heart in lead I, a V R, and V 1. The horizontal axis represents time in seconds, and the vertical axis represents electrical potential in millivolts. Panel B: A line graph showing the electrical activity of the heart in lead II, a V L, and V 2. The horizontal axis represents time in seconds, and the vertical axis represents electrical potential in millivolts. Panel C: A line graph showing the electrical activity of the heart in lead III, a V F, and V 3. The horizontal axis represents time in seconds, and the vertical axis represents electrical potential in millivolts. Panel D: A line graph showing the electrical activity of the heart in lead II, V 4, V 5, and V 6. The horizontal axis represents time in seconds, and the vertical axis represents electrical potential in millivolts.

The 24-hour Holter recording showed sinus rhythm as the baseline rhythm, first-degree atrioventricular block (PR interval 196 ms), frequent second-degree Mobitz type I atrioventricular block, and rare Mobitz type II atrioventricular block (Figure 2). Following discontinuation of transdermal fentanyl, sinus rhythm became progressively more dominant. On day 4 after discontinuation, repeat Holter monitoring showed shortening of the PR interval, rare episodes of first-degree atrioventricular block, and approximately 10 minutes in total of second-degree Mobitz type I atrioventricular block; Mobitz type II atrioventricular block was no longer observed. By day 7 after cessation of fentanyl, the patient had completely returned to sinus rhythm (Figure 3). During follow-up, sinus rhythm persisted, and no recurrence of atrioventricular block was detected.

Figure 2.

Blocks in the 24-hour rhythm Holter recording. ( a ) first-degree AV block. ( b ) second-degree Mobitz type 1 AV block. ( c ) second-degree Mobitz type 2 AV block.

Figure 3.

Sinus rhythm after the effect of transdermal fentanyl wears off.

Discussion

Fentanyl is a synthetic opioid with short-acting analgesic properties when administered intravenously or subcutaneously. Its low molecular weight, high lipophilicity, and potent analgesic effect enable transdermal use.Reference Payne, Chandler and Einhaus ¹ Several studies have demonstrated that transdermal fentanyl significantly reduces pain severity, particularly in patients with chronic cancer pain. ^{Reference Berde, Billett, Collins, Pizzo and Poplack2–Reference Bilen, Ali and Alkan4} In our patient, transdermal fentanyl was initiated for chronic pain management associated with non-Hodgkin lymphoma.

Transdermal administration offers advantages such as ease of use and stable plasma drug levels. However, the skin acts not only as a passive diffusion barrier but also as a drug reservoir. After application, minimal analgesic effect typically appears within 12–40 hours, and maximum serum concentration is reached within approximately 12–48 hours. A steady state is achieved by the third day and maintained as long as new patches are applied. Serum concentrations gradually decrease and disappear over a 72-hour period. ^{Reference Flaherty, Szekely and Read5} Transdermal fentanyl is generally initiated at doses of 25–50 micrograms/hour due to respiratory side effects. ^{Reference Sevarino, Naulty and Sinatra6} In our case, despite administration within the recommended dose range, progressive improvement in cardiac rhythm was observed beginning on the fourth day after discontinuation, with complete restoration of sinus rhythm.

The most serious complication of opioid therapy is hypoventilation. Other adverse effects include nausea, vomiting, constipation, skin irritation, and tolerance. ^{Reference McNikol, Horowicz-Mehler and Fisk3} Studies have shown that transdermal fentanyl does not significantly impair psychomotor or cognitive functions and does not markedly restrict daily activities. ^{Reference Sabatowski, Schwalen and Rettig7,Reference Haythornthwaite, Menefee and Quatrano-Piacentini8} Consequently, its use has become increasingly widespread. Studies in adults and animal models have demonstrated that multiple sedative agents, including intravenous fentanyl, may lead to atrioventricular block. ^{Reference Cho, Song and Lim9–Reference Rahhal, Aljundi and Arabi11} However, there are no reports specifically addressing this effect with transdermal fentanyl. In our patient, the development of various degrees of atrioventricular block following initiation of transdermal fentanyl, along with progressive resolution and complete return to sinus rhythm after discontinuation, strongly suggests a drug-related mechanism. The exclusion of alternative causes such as myocarditis, electrolyte imbalance, or structural cardiac pathology further supports this association. The temporal relationship and reversibility after cessation are noteworthy.

This case demonstrates that even at recommended doses, transdermal fentanyl may cause rare but clinically significant cardiac conduction disturbances. We emphasise the importance of regular cardiac monitoring and electrocardiographic follow-up during transdermal opioid therapy, particularly in paediatric oncology patients.