Electrocardiographic findings of the effects of beta-blockers

CASE 1

CLINICAL PRESENTATION

An 85-year-old woman presented to the emergency department with drowsiness on a background of functional decline of two weeks’ duration. Her medical history was significant for hypertension and hyperlipidaemia, for which she was on regular follow-up. Medications included amlodipine 10 mg OM (every morning), atenolol 100 mg OM, atorvastatin 20 mg ON, frusemide 40 mg OM, prazosin 0.5 mg BD (twice daily) and valsartan 160 mg OM. The patient was drowsy with Kussmaul breathing prior to a transient period of asystole noted on the cardiac monitor. Immediate resuscitation was performed with return of spontaneous circulation after 10 seconds.

Initial investigations showed decompensated metabolic acidosis (pH 7.14, partial pressure of carbon dioxide 24 mmHg, bicarbonate 8.4mmol/L) with hyperkalaemia (6.9 mmol/L), for which she was treated with calcium gluconate, insulin and dextrose. What did her admission electrocardiogram (ECG) show (Fig. 1)?

Fig. 1

Case 1: Initial ECG on admission performed after resuscitation.

ECG INTERPRETATION

Fig. 1 shows sinus node dysfunction with intermittent sinus P waves (black arrow) with first-degree atrioventricular block (double-headed arrow), as well as intermittent junctional escape beats (white arrow). Tall, tented T-waves (arrowhead) were observed in leads V2 and V3.

Fig. 2 shows a rhythm strip obtained from the cardiac monitor when the patient was paced transcutaneously. Pacing spikes are observed before each QRS complex (arrows).

Fig. 2

Case 1: Rhythm strip on ECG shows transcutaneous pacing, with arrows indicating pacing spikes.

CLINICAL COURSE

The patient’s hypotensive and bradycardic episodes persisted following resuscitation despite initiation and titration of intravenous dopamine to 20 mcg/kg/min. Further investigations revealed acute kidney injury, with an elevated creatinine level of 853 mmol/L from a baseline of 65 mmol/L. The patient was then intubated for airway protection, started on inotropic support and administered intravenous glucagon. She was also commenced on transcutaneous pacing (TCP) at 70 beats per minute (bpm) (Fig. 2). The working diagnosis was cardiogenic shock secondary to the beta-blocker (BB) atenolol, which was attributed to acute kidney injury. The patient was then admitted to the intensive care unit, where continuous renal replacement therapy (CRRT) was initiated.

The patient’s intrinsic cardiac rhythm improved following two days of CRRT, with an improvement in her heart rate. The TCP backup pacing and inotropes were gradually weaned and stopped after four days, and the patient became haemodynamically stable without support. Atenolol was also stopped since admission.

CASE 2

CLINICAL PRESENTATION

A 53-year-old man with a significant medical history of Type 2 diabetes mellitus, hypertension, hyperlipidaemia, chronic kidney disease and ischaemic heart disease presented with non-ST elevation myocardial infarction on a background of septic shock and acute-on-chronic kidney injury/disease (AoCKD). His medications included aspirin 100 mg OM, clopidogrel 75 mg OM, carvedilol 6.25 mg BD, atorvastatin 40 mg ON and frusemide 80 mg TDS (three times a day). The patient developed haemodynamically significant bradycardia despite being administered intravenous dopamine of 20 mcg/kg/min. What does the ECG (Fig. 3) that was obtained at the onset of deterioration show?

Fig. 3

Case 2: ECG at the onset of clinical deterioration.

ECG INTERPRETATION

Fig. 3 shows marked sinus bradycardia at a rate of 40 bpm, with first-degree heart block. There is a P wave (circles) preceding each QRS complex, and the PR interval (double-headed arrow) is prolonged at approximately 220 ms.

Fig. 4 shows a ventricular-paced rhythm, as evidenced by the small pacing spike (black arrows) just preceding its QRS complex (white arrowheads). We were able to localise the position of the pacing wire in the right ventricular (RV) apex owing to the left bundle branch block morphology of depolarisation on the precordial leads (black arrowheads) and negative QRS polarity on the inferior limb leads II, III and aVF (white arrows). The RV apex location of the transvenous pacing (TVP) tip was confirmed via chest radiograph, as observed in Fig. 5 (circle).

Fig. 4

Case 2: Electrocardiogram after transvenous pacing.

Fig. 5

Case 2: Chest radiograph after transvenous pacing.

CLINICAL COURSE

The patient remained haemodynamically unstable on intravenous infusion of dopamine of 20 mcg/kg/min and was started on TCP. This resulted in improvement of haemodynamics. Laboratory investigations revealed progression of AoCKD. Review of drug charts also revealed that the patient had been consistently administered carvedilol 6.25 mg BD during his inpatient stay. A diagnosis of haemodynamically significant bradycardia secondary to carvedilol retention on a background of poor renal clearance owing to AoCKD was established. The patient was sent to the coronary care unit for immediate TVP to augment cardiac output.

DISCUSSION

BBs are commonly used in general practice for a variety of medical conditions. Major society guidelines have indicated the use of BBs for the management of stable ischaemic heart disease, acute coronary syndrome,(1-3) atrial fibrillation,(4) atrial flutter,(4) supraventricular tachycardia,(5) ventricular tachycardia,(6) hypertrophic cardiomyopathy(7) and heart failure.(8)

Pharmacokinetics

The pharmacokinetic properties of BBs can be broadly divided into lipophilic and hydrophilic drugs. Lipophilic drugs (e.g. metoprolol, propranolol and timolol) are absorbed from the enteral route but undergo extensive hepatic first-pass metabolism, leading to low oral bioavailability (10%–30%). Hence, these drugs may accumulate in patients with reduced hepatic perfusion (e.g. elderly patients, or those with congestive cardiac failure or liver cirrhosis) (Table I). They have shorter elimination half-lives (1–5 hours) and may penetrate the blood-brain barrier, accounting for a greater incidence of central side effects.(9)

Table I

Pharmacokinetics of some commonly used beta-blockers.(10)

Conversely, hydrophilic drugs (e.g. atenolol and esmolol) are absorbed in their entirety from the gastrointestinal tract and are renally excreted unchanged or as active metabolites. These drugs do not readily cross the blood-brain barrier and have longer elimination half-lives (6–24 hours), which are further prolonged in case of a reduction in glomerular filtration rate (GFR) (i.e. elderly individuals, patients with renal insufficiency) (Table II).(9,10)

Table II

Properties of beta-blockers in relation to renal function.(10)

BBs such as bisoprolol exhibit equal hepatic and renal clearance (balanced clearance),(9) while carvedilol has a low oral bioavailability owing to its extensive first-pass metabolism. It binds to plasma proteins and is eliminated hepatically.(11)

CONCLUSION

In conclusion, despite the vast therapeutic indications of BBs, their use is associated with potentially life-threatening risks. Prompt recognition of the signs and symptoms as well as the predisposing factor of BB-related toxicities and instituting appropriate emergency medical therapy are of utmost importance in the face of an ageing population with multiple comorbidities and polypharmacy.