Patients undergoing surgery are often exposed to QT-inciting factors that may increase the risk for complications. We evaluated the clinical characteristics and outcomes of patients with QTc ≥500 ms within the first 24 hours after surgery as identified by an institution-wide electrocardiogram alert system. From November 2010 to June 2011, 470 patients exhibited an electrocardiographically isolated QTc ≥500 ms. QT prolongation after surgery was the setting for >1 of every 10 QTc alerts (59 patients). We determined the presence of QT prolonging medical conditions, drugs, electrolyte abnormalities, and the surgical patient’s clinical outcome. The average preoperative QTc of the 59 patients demonstrating perioperative QT prolongation was 463 ± 56 ms with a postoperative QTc increase of 54 ± 37 ms. Most patients (n = 48, 83%) had ≥1 known QT-inciting factor before surgery. Compared with presurgical findings, there was a significant increase in pro-QTc score after surgery (1.8 ± 1.5 vs 3.5 ± 2.0, p <0.01) indicating a greater burden of perioperative QT-inciting factors. In conclusion, nearly all cases of QT prolongation could be explained by known etiologic or iatrogenic factors suggesting that maladaptive cardiac repolarization is most likely not a transient, postoperative stress response and may be avoided by altering clinical management.
QT prolongation on an electrocardiogram (ECG) is associated with increased all-cause cardiovascular mortality, such as sudden cardiac death (SCD) and stroke, within the general population. QT-prolongation is associated with a number of co-morbidities, electrolyte disturbances, and QT-prolonging drugs. Many of these QT-prolonging factors are modifiable if the provider is aware of their presence. The Mayo Clinic in Rochester, Minnesota, recently implemented an institution-wide QT alert system that automatically notifies providers if a patient’s ECG exhibits QT prolongation. Recent evaluation of the alert system’s first months of implementation provided the spectrum and prevalence of QT-prolonging causes and showed a clear correlation between a pro-QTc score (created from the sum of QT-inciting factors) and patient mortality. Furthermore, analysis of the alerted ECGs showed QT prolongation to be a common occurrence in the postsurgical period. Being able to identify these occurrences as either transient postoperative stress responses or attributable to already known QT-inciting factors may help reduce the possibility of fatal arrhythmias in the perioperative period. Herein, we performed a subset analysis on those patients whose ECG provoked a QT alert within 24 hours of surgery.
Methods
All ECGs performed at Mayo Clinic, Rochester, Minnesota from November 2010 to June 2011 were analyzed by a QT alert system algorithm previously described by Haugaa et al. All qualifying alerted ECGs were then analyzed by a research cardiologist blinded to the automated QT interval measurements. Retrospective analysis was performed to identify which of these alerted ECGs occurred within 24 hours after surgery, and the medical records of this subset of patients were reviewed for possible surgical causes of the QT prolongation. The data extracted included age, gender, ethnicity, admission diagnosis, date, length and type of procedure performed, administered medications (both intraoperatively and perioperatively), electrolyte laboratory values, and any presurgical and postsurgical ECG findings.
Main admission diagnoses were categorized into 9 groups: cardiovascular, gastrointestinal, neurological, renal, diabetes, malignancy, pulmonary, infectious, and trauma. Procedure types were similarly categorized into the following groups: general, cardiac, transplant, neurologic, and other. The length of procedure was defined as the time between the beginning and end of general anesthetic induction.
All medications administered within 7 days before and after the alerted ECG were reviewed and all known QT-prolonging medications were noted. These medications were grouped into 2 tiers using the groupings categorized by the CredibleMeds QT drug list. Tier 1 drugs have a risk of TdP and tier 2 drugs prolong the QT interval and have possible risk of TdP. Medications were also grouped into intraoperative and hospital administered categories for comparison.
Serum potassium, ionized calcium, and magnesium levels before, during, and after surgery were assessed when available. Per Mayo Clinic reference values, hypokalemia was defined as <3.6 mmol/l, hypomagnesemia as <1.7 mg/dl, and hypocalcemia as <4.65 mg/dl.
A pro-QTc score was assigned to each patient both preoperatively and postoperatively. This score was created by assigning one point for each of the following findings: presence of QT-affecting clinical diagnosis, QT-prolonging electrolyte disturbances, and/or QT prolonging medications present on the CredibleMeds drug list. QT-affecting clinical diagnoses and conditions included acute coronary syndrome, anorexia nervosa, bradycardia, cardiac heart failure, diabetes mellitus (type 1 and 2), hypertrophic cardiomyopathy, hypoglycemia, intoxication with QT-prolonging drug (<24 hours), long QT syndrome, pheochromocytoma, renal dialysis, within 7 days after cardioversion, radiofrequency ablation or maze procedure, within 24 hours of cardiac arrest, within 24 hours of syncope or seizure, and within 7 days after stroke, subarachnoid hemorrhage, and head trauma. Mortality was assessed by inpatient hospital records, obtaining a death certificate, physician’s record of death diagnosis, or the patient’s relatives’ communication of death diagnosis.
Characteristics of those patients with a postoperative QTc alert were compared with all other patients with alerted ECGs using a dependent Student t test for continuous variables or Fisher’s exact test for nominal value. p values <0.05 were considered to be statistically significant. All statistics were performed using JMP software version 9.0.1.
Results
Of the 86,107 ECGs performed on 52,579 unique patients from November 2010 to June 2011, there were 470 patients with electrocardiographically isolated QTc ≥500 ms. During this time span, there were 13,031 total procedures performed at our institution. A QTc alert occurred within 24 hours of surgery for 59 of the 470 alerted patients, which represented 0.5% (59 of 13,031) of all surgical patients. The demographics of this postoperative QTc study cohort are summarized in Table 1 .
| Variable | Total (n = 470) | Post-Op (n = 59) | Other (n = 411) | P value |
|---|---|---|---|---|
| Age (years) | 55 ± 24 | 62 ± 21 | 54 ± 25 | 0.01 |
| Women | 263 (56%) | 31 (36%) | 232 (57%) | 0.6 |
| White | 430 (91%) | 53 (90%) | 377 (92%) | 0.6 |
| QRS duration (ms) | 92 ± 14 | 92 ± 14 | 91 ± 14 | 0.8 |
| QTc (ms) | 517 ± 33 | 516 ± 21 | 517 ± 34 | 0.9 |
| ≥1 QT prolonging factor | 456 (97%) | 48 (83%) | 404 (98%) | <0.001 |
| QT-associated comorbidity | 271 (58%) | 26 (44%) | 245 (60%) | 0.03 |
| Hypokalemia (K <3.6 mmol/L) | 121 (26%) | 5 (9%) | 102 (29%) | 0.4 |
| Hypomagnesemia (Mg <1.7 mg/dL) | 74 (16%) | 2 (3%) | 59 (21%) | 0.05 |
| Hypocalcemia (Ca <4.65mg/dL) | 131 (28%) | 10 (17%) | 101 (55%) | 0.09 |
| QT-prolonging medications | 310 (66%) | 36 (61%) | 242 (67%) | 0.08 |
| Pro-QTc score | 2.5 ± 1.6 | 1.8 ± 1.5 | 2.5 ± 1.6 | 0.8 |
| Mortality | 105 (22%) | 13 (22%) | 92 (22%) | 1 |
Overall, 48 patients (83%) had ≥1 QT-prolonging inciting factor present before surgery leading to a mean pro-QTc score of 1.8 ± 1.5. Of these, 26 patients (44%) had a QT-prolonging co-morbidity before surgery. Preoperative potassium, magnesium, and calcium levels were available for 50, 18, and 27 patients, respectively. Preoperative hypokalemia was present in 5 patients, hypomagnesemia in 2 patients, and hypocalcemia in 10 patients. Thirty-six patients (61%) were on a QT-prolonging drug before their procedure. These medications were given to 19 patients during their hospital stay and 17 were prescribed in the outpatient setting. Overall, 13 patients (22%) died over a mean follow-up of 208 days (range 1 to 517). A cause of death was identified in 9 patients (69%) with the most common cause being malignancy (n = 4, 31%). Importantly, none of the patients died in the postoperative period.
Compared to the larger group of 470 patients, this perioperative cohort was significantly older (62 ± 21 vs 54 ± 25 years, p = 0.01), but no other differences between clinical parameters or prevalence of components of the QT score were observed ( Figure 1 ).
Among this subset of surgical patients, most procedures performed were cardiac (n = 27, 46%), followed by general (n = 16, 27%), transplant (n = 6, 10%), neurology (n = 4, 7%), vascular (n = 3, 2%), urology (n = 2, 1%), otorhinolaryngology (n = 2, 1%), ophthalmology (n = 2, 1%), and orthopedic (n = 2, 1%, Figure 1 ). The preoperative ECGs displayed an average QTc of 463 ± 56 ms, whereas the alerted postoperative ECGs demonstrated an average QTc of 516 ± 21 ms (a mean increase of 54 ± 37 ms, p <0.001) and QRS of 92 ± 14 ms ( Figure 2 ). Long-term follow-up showed a significant reduction of QTc to 473 ± 49 ms (p <0.001) from the postoperative peak QTc which was comparable to their preoperative QTc.
Compared with presurgical findings, there was a significant increase in pro-QTc score after surgery (1.8 ± 1.5 vs 3.5 ± 2.0, p <0.001, Figure 3 ) indicating a greater burden of perioperative QT-inciting factors. Although 9 (15%) patients had no change in pro-QTc score and 1 (2%) had a pro-QTc score improvement after surgery, the remaining 49 (83%) patients had ≥1 QT-associated risk factor added perioperatively and 30 (51%) patients had >1 risk factor added postoperatively ( Figure 3 ). In total, 7 patients (12%) experienced new-onset hypokalemia, 13 patients (22%) experienced new-onset hypomagnesemia, and 24 patients (41%) experienced new-onset hypocalcemia after surgery. Additional QT-prolonging medications were given during surgery to 4 patients (7%) already using QT-prolonging medications before surgery and 5 patients (8%) were given a known QT-prolonging medication intraoperatively for the first time. Of the medications administered, 14 were CredibleMeds tier 1 drugs and 16 were tier 2 drugs. The most common tier 1 and tier 2 drugs administered were amiodarone (9 patients) and ondansetron (11 patients), respectively. Of those patients receiving amiodarone, 7 were concomitantly given an additional QT-prolonging drug.
