Abstract
Background:
While perioperative medical management during total knee arthroplasty (TKA) has improved, there is limited literature characterizing outcomes of patients with pulmonary hypertension (HTN). This study examined mortality, medical complications, implant survivorship, and clinical outcomes in this medically complex cohort.
Methods:
We identified 887 patients with pulmonary HTN who underwent 881 primary TKAs and 228 revision TKAs from 2000–2016 at a tertiary care center. Patients were followed up at regular intervals until death, revision surgery, or last clinical follow-up. Perioperative medical complications were individually reviewed. The risk of death was examined by calculating standardized mortality ratios and Cox proportional hazards regression models. Cumulative incidence analysis was used for reporting mortality, revision, and reoperation with death as a competing risk.
Results:
The 90-day mortality was 0.7% and 4.8% for primary and revision TKAs, respectively. The risk of death was two-fold higher compared to primary (hazard ratio 2.54, 95% CI: 2.12 – 3.05) and revision (hazard ratio 2.16, 95% CI: 1.78 – 2.62) TKA patients without pulmonary HTN. Rate of medical complications within 90 days from surgery were 6.5% and 14% in primary and revision TKAs. The 10-year cumulative incidence of any revision was 5% and 16% in primaries and revisions, respectively.
Conclusion:
Patients with pulmonary HTN undergoing primary and revision TKAs had excess risk of death and experience a high rate of medical complications within 90 days of surgery. Counseling of risks, medical optimization, and referral to tertiary centers should be considered.
Level of Evidence:
Level IV
Keywords: Total knee arthroplasty (TKA), revision total knee arthroplasty (TKA), pulmonary hypertension, complications, mortality
INTRODUCTION
Total knee arthroplasty (TKA) remains one of the most successful procedures with increasing volume annually [1]. As a result of a growing aged United States (US) population and improving perioperative medical management, the number of patients with complex medical comorbidities who undergo TKA are expected to increase. Pulmonary hypertension (HTN) is a relatively common comorbidity with increasing incidence world-wide [2]. The incidence of pulmonary HTN increased between 2003 and 2012 from 24.1 to 28.7 cases per 100,000 persons, and a diagnosis of pulmonary HTN increases the one-year standardized mortality ratio by 7.2 [2].
Pulmonary HTN is defined as resting pulmonary arterial pressure above 25 mm Hg and typically diagnosed on an echocardiogram. An echocardiogram study can evaluate right ventricular systolic pressure and, by extension, estimate pulmonary arterial pressure. Pulmonary HTN is known to increase complications in patients undergoing non-cardiac surgeries and was found to be a risk factor for periprosthetic joint infection (PJI) in total hip arthroplasties (THAs) [2–7]. While patients with pulmonary HTN undergoing primary and revision TKAs have theoretically higher complication rates, there is a paucity of data analyzing outcomes in this complex patient cohort.
As such, the purpose of this study was to review the outcomes of primary and revision TKAs in a large series of patients with pulmonary HTN. Specifically, we examined mortality, perioperative medical complications, implant survivorship free from revision and reoperation, and clinical outcomes.
PATIENTS AND METHODS
After obtaining institutional review board approval, our institutional total joint registry was used to identify all patients aged >18 years undergoing a primary or revision TKA from 2000 to 2016 with a concomitant diagnosis of pulmonary HTN prior to surgery or within 1 year of surgery. Prior to surgery, all patients underwent preoperative medical clearance. Patients deemed high-risk were sent to cardiology and/or pulmonology for further review and optimization. Staging and workup for pulmonary HTN varied during the study period with many patients diagnosed at outside medical institutions and confirmed at preoperative anesthesia evaluation. Therefore, patients were included based on final diagnosis by anesthesia and/or medical doctor notes in the institutional medical record and were not stratified according to severity of pulmonary HTN. There were 20,122 primary TKA and 4,927 revision TKA procedures performed at the institution during the study period. Of these, 688 patients who underwent 881 primary TKAs and 207 patients who underwent 228 revision TKAs had a diagnosis of pulmonary hypertension and were identified for review. There were 15 simultaneous bilateral procedures and 186 staged bilateral procedures with median time to second procedure of 353 days. There were 3 bilateral simultaneous revision procedures and 18 staged bilateral revisions with median time to second procedure of 445 days. Of these procedures, 90 (8%) had less than 2 years of follow-up, and 80 (7%) died prior to two years of follow-up. The remaining 939 (85%) procedures had a mean follow-up of 6 years (range, 2 – 16 years).
For primary TKAs, the mean age was 72 years (range, 30 – 98 years) and 558 patients (63%) were female (Table 1). The mean body mass index (BMI) was 34 kg/m2 (range, 17 – 69 kg/m2). Pulmonary HTN was diagnosed at a mean of 4 years (range, 1 – 26 years) before TKA. Median American Society of Anesthesiologists (ASA) score was 3 with 69% of patients having an ASA score 3 or higher, while 31% were ASA score 2 or less.
Table 1.
Patient Demographics
| Primary TKA | Revision TKA | |
|---|---|---|
| Age in Year, Mean (Range) | 72 (30–98) | 71.5 (18–93) |
| Sex, % female | 63.3% | 55.0% |
| BMI in kg/m2, Mean (Range) | 34.1 (17.1 – 69.1) | 34.8 (17.5 – 70.5) |
| Years from pulmonary HTN diagnosis to TKA, Mean (Range) | 3.0 (25.9 – 0.6) | 2.9 (15.2 – −1.0) |
| ASA score | ||
| <3 | 31% | 22% |
| ≥3 | 69% | 78% |
TKA = total knee arthroplasty; BMI = body mass index, HTN = hypertension; ASA = American Society of Anesthesiologists
For revision TKAs, the mean age was 72 years (range, 18 – 93 years) with 126 patients (55%) being female (Table 1). The mean BMI was 35 kg/m2 (range, 18 – 71 kg/m2). Pulmonary HTN diagnosis was made a mean of 3 years (range, −1 – 15 years) before the revision TKA. The median ASA score was 3, with 78% of patients were an ASA score 3 or higher, while 22% (n = 42) were ASA score 2 or less.
Reoperation included any surgical intervention with or without alteration of the implants. Revision was defined as a surgical intervention involving replacement of at least one component. Indications for revision TKA included aseptic loosening (54 patients, 24%), chronic PJI and the reimplantation stage of a two-stage exchange arthroplasty (48 patients, 21%), acute PJI (47 patients, 21%), instability (26 patients, 11%), osteolysis/wear (25 patients, 12%), periprosthetic fracture (19 patients, 8%), conversion of unicompartmental arthroplasty to total knee arthroplasty (5 patients, 2%), and acquired idiopathic stiffness (4 patients, 2%).
Patient demographics and perioperative details were retrieved from the medical record, which was specifically reviewed for the purpose of this study. Clinical outcomes were assessed via Knee Society scores (KSS) both preoperatively and at multiple time points postoperatively [8].
Statistical Analysis
First, we performed an external mortality comparison to the US general population mortality as well as mortality in primary and revision TKA. The observed survival of pulmonary HTN patients was compared with the expected survival of the age-, sex-, and calendar-year matched US total population. These observed and expected survival curves were compared using one-sample log-rank tests. Standardized mortality ratios (observed deaths/expected deaths) were generated and reported with 95% confidence intervals. Secondly, the risk of death after TKA in patients with pulmonary HTN was compared to an external cohort of patients without pulmonary HTN undergoing primary and revision TKA using Cox proportional hazards regression, adjusting for age, sex and calendar year using data from previously published studies [9, 10]. Hazard ratios are reported with 95% confidence intervals. Third, cumulative incidence analysis was used to describe mortality after primary and revision TKAs. The risk of revision and reoperation were assessed with a competing risk analysis, with death as competing risk, due to the high perioperative mortality and the extended time frame of the study. Clinical outcome scores were available for 789 primary and 159 revision TKAs and analyzed with student t-tests. Significance was set at p<0.05. All statistical analysis were performed using JMP software (SAS, Cary, NC)
RESULTS
Mortality
The standardized mortality ratio for patients with pulmonary HTN undergoing primary TKA and revision TKA compared to the general population was 1.14 (95% CI 1.01 – 1.28, p=0.03) and 2.01 (95% CI 1.01 – 1.28, p<0.001), respectively. Adjusting for age, sex, calendar year, the hazard ratio (HR) of death for patients with pulmonary HTN following primary and revision TKA compared to patients without pulmonary HTN following primary and revision TKA was 2.54 (95% CI 2.12 – 3.05, p <0.001) and 2.16 (95% CI 1.78 – 2.62, p <0.001), respectively. Figure 1 shows cumulative incidence of death following primary and revision TKA. Ninety-day mortality was 0.7% and 4.8% for primary and revision TKAs, respectively (Table 2). Six patients died within 90 days of their primary TKA from cardiac arrest (n = 2), respiratory failure (n = 2), pneumonia (n=1), and unknown causes (n = 1). Eleven patients died within 90 days of their revision TKA from sepsis (n = 4), respiratory failure (n = 2), unknown causes (n=2), arrhythmia (n=1), heart failure (n=1), and gastrointestinal bleeding (n=1). PJI was the surgical indication for all revision TKA cases associated with mortality within 90 days. Nine of the 11 perioperative deaths following revision TKA were acute PJIs that underwent irrigation and debridement with modular component exchange, while 2 where chronic PJIs treated with modular and non-modular component exchange.
Figure 1.
Cumulative incidence of death after primary and revision TKA in patients with pulmonary hypertension.
Table 2.
Perioperative medical complications within 90 days of primary and revision TKA in patients with pulmonary hypertension
| Outcomes | Primary TKA (N=881) | Revision TKA (N=228) | Entire cohort (N=1109) |
|---|---|---|---|
| Total non-mortality complications, n (%) | 51 (5.79%) | 21 (9.21%) | 72 (6.49%) |
| Arrhythmia | 19 (2.16%) | 8 (3.51%) | 27 (2.43%) |
| Deep Vein Thrombosis | 9 (1.02%) | 1 (0.44%) | 10 (0.90%) |
| Respiratory failure/ARDS | 7 (0.79%) | 2 (0.88%) | 9 (0.81%) |
| Myocardial infarction | 6 (0.68%) | 0 (0.00%) | 6 (0.54%) |
| Sepsis | 0 (0.00%) | 6 (2.63%) | 5 (0.45%) |
| Pneumonia | 4 (0.45%) | 0 (0.00%) | 4 (0.36%) |
| Pulmonary Embolism | 3 (0.34%) | 1 (0.44%) | 4 (0.36%) |
| Stroke/TIA | 1 (0.11%) | 1 (0.44%) | 2 (0.18%) |
| Heart Failure | 1 (0.11%) | 1 (0.44%) | 2 (0.18%) |
| GI Bleed | 0 (0.00%) | 1 (0.44%) | 1 (0.09%) |
| Syncope | 1 (0.11%) | 0 (0.00%) | 1 (0.09%) |
| 90-day mortality | 6 (0.68%) | 11 (4.82%) | 17 (1.53%) |
| Total medical complications (death included) | 57 (6.47%) | 32 (14.04%) | 89 (8.03%) |
| Postoperative ICU admission, n (%) | 19 (2.16%) | 11 (4.82%) | 30 (2.71%) |
| Readmission for medical problem, n (%) | 10 (1.14%) | 0 (0.00%) | 10 (0.90%) |
| Cases with wound complications, n (%) | 21 (2.38%) | 10 (4.39%) | 31 (2.80%) |
ARDS = Acute respiratory distress syndrome, TIA = Transient ischemic attack, ICU = Intensive care unit
The cumulative incidence of death at 2 and 10 years were 5.6% and 59% for primary TKAs, respectively (Figure 1). The cumulative incidences of death at 2 and 10 years were 20% and 70% for revision TKAs, respectively.
Perioperative Medical Complications
The incidence of perioperative medical complications, including death, was 6.5% in the primary TKA group and 14% in revision TKA group (Table 2). Regarding non-mortality complications, the most common were cardiac arrhythmias (2.2% for primary TKAs, 3.5% for revision TKAs), venous thromboses (1% for primary TKAs, 0.4% for revision TKAs), respiratory failure/acute respiratory distress syndrome (ARDS) (0.8% for primary TKAs, 0.9% for revision TKAs), and myocardial infarction (0.7% for primary TKAs, 0% for revision TKAs). Admission to the intensive care unit (ICU) was required postoperatively in 2.2% (19 patients) of primary and 4.8% (11 patients) of revision cases. Hospital readmission occurred in 1.1% of primary TKA cases, but in no revision TKA cases. There was also a high number of superficial wound complications with 2.4% (21 patients) of primaries and 4.4% (10 patients) of revisions affected. Two hundred and twenty-three patients (25%) who underwent primary TKA received an allogeneic blood transfusion during their hospitalization while 15 patients (2%) received an autologous blood transfusion. Eighty-five patients (37%) who underwent revision TKA received an allogeneic blood transfusion during their hospitalization while 28 patients (13%) received an autologous blood transfusion.
Cumulative Incidence of Any Revision and Reoperation
The cumulative incidence of any revision after primary TKA with death as the competing risk at 5 and 10 years was 3.9% (95% CI 2.8% – 5.5%) and 4.9% (95% CI 3.5% – 6.8%), respectively (Figure 2). There were 37 total revisions after primary TKA during the study period. Indications for revision after primary TKA included acute PJI (14 cases, 37%), chronic PJI (7 cases, 19%), periprosthetic fracture (6 cases; 16%), instability (5 cases, 14%), aseptic loosening (3 cases, 8%), and wear/osteolysis (2 cases, 5%). The 10-year cumulative incidence of any reoperation after primary TKA with death as the competing risk was 9.9% (95% CI 7.9% – 12.4%). There were a total of 76 reoperations, with 39 (51%) requiring no component exchange. Indications for reoperation after primary TKA without component exchange included superficial wound complication (22 cases, 56%), acquired idiopathic stiffness (9 cases, 23%), and periprosthetic fracture (8 cases, 21%).
Figure 2.
Competing risk analysis of revision TKA after primary or revision TKA.
The cumulative incidences of any re-revision after revision TKA with death as the competing risk at 5 and 10 years were 14.4% (95% CI 10.3% – 20.1%) and 16.1% (95% CI 11.7% – 22.4%), respectively (Figure 2). There were a total of 32 re-revision after revision TKA. Indications for re-revision TKA with non-modular component exchange included PJI (16 cases, 50%), instability (7 cases, 22%), aseptic loosening (6 cases, 19%), and wear/osteolysis (3 cases, 9%). The 10-year cumulative incidence of any reoperation after revision TKA with death as competing risk was 19.8% (95% CI 14.9 – 26.3%). There were a total of 40 reoperations after revision TKA, with 8 (20%) requiring no component exchange. Indications for reoperation after revision TKA without component exchange included periprosthetic fracture (4 cases, 50%), acquired idiopathic stiffness (3 cases, 38%), and superficial wound dehiscence (1 case, 12%).
Clinical Outcomes
For primary TKA, KSSs improved from a mean of 39 (range, 0 – 93) preoperatively to mean of 84 (range, 26 – 95; p < 0.001) postoperatively. For revision TKAs, KSSs improved from a mean of 42 (range, 0 – 94) preoperatively to 76 (range, 17 – 95; p<0.001) postoperatively.
DISCUSSION
The demand for primary and revision TKAs, as well as the incidence of pulmonary hypertension, are both increasing. Based on the outcomes of patients with pulmonary hypertension undergoing non-cardiac surgeries, we anticipated inferior outcomes, including death, in those patients undergoing primary and revision TKAs [3, 4, 7]. In the current study, we found a high rate of 90-day mortality for primary and revision TKAs. Furthermore, we found a high rate of ICU admission and perioperative medical complications, most commonly cardiac arrhythmias. This highlights the need for appropriate counseling, medical optimization, and likely referral to tertiary care centers with additional available resources for TKA in this medically complex patient population.
A major concern in this patient population is perioperative mortality. The 90-day mortality after primary and revision TKAs in the general population has been estimated to be 0.79% and 0.7%, respectively, and similar to that found after primary TKA in this study at 0.68% [11–13]. However, perioperative mortality was markedly greater for revision TKA at 4.8%. Notably, the indication for revision TKA in all cases of death within 90 days was PJI. PJI is an independent risk factor for mortality with prior studies showing a 3.9% in-hospital mortality rate and 6–18% mortality rate in the years following two-stage exchange for infected TKA [14–17]. Additionally, admission to the ICU following surgical treatment of acute or chronic PJI was associated with a 21% mortality rate [18]. In pulmonary HTN patients undergoing non-cardiac and non-obstetric surgery, Meyer et al. [4] showed an overall perioperative mortality rate of 3.5%, with that mortality rate increasing to 15% in emergency procedures. This highlights how perioperative mortality in patients with pulmonary HTN is a problem across all surgical disciplines and made more precarious in the setting of PJI which is already carries a significant mortality risk.
In terms of mortality risk outside of the perioperative period, patients have been shown to have lower mortality for roughly 8 years following primary TKA compared to the general population and either similar or greater mortality risk than the general population following revision TKA depending on revision indication [9, 10]. In comparison, our study showed the mortality risk in patients with pulmonary HTN undergoing primary and revision TKA was significantly greater than the general population, and was over twice the mortality risk of patients without pulmonary HTN undergoing primary and revision TKA. Shroder et al.[19] found the 5-year mortality after total joint arthroplasty was 11%, whereas the current study demonstrated a higher 5-year mortality of 21% and 46% for primary and revision TKAs, respectively. The mortality rates at 5 and 10 years in this population are consistent with the natural history of pulmonary HTN where 5-year mortality estimates following diagnosis of pulmonary HTN depend on diagnostic subgroup but range between 35.5% and 43% [20]. The slightly superior 5-year mortality rate for patients in this study compared to pulmonary HTN patients at large may be related to this being a select cohort deemed healthy enough for an elective surgical procedure.
Outside of perioperative death, there is concern for medical complications brought on by the perioperative stress of surgery. Prior studies in patients undergoing non-cardiac surgery with pulmonary HTN have shown an increased incidence of various medical complications [2, 3]. When comparing the postoperative medical complications in the general population undergoing TKA to this cohort, there are similar rates of deep vein thrombosis, stroke, and sepsis, with an increased rate of myocardial infarctions, superficial wound complications, and postoperative ICU admission [21]. The rate of blood transfusions during the perioperative period was also high and is a notable risk factor for medical complications as well as subsequent prosthetic joint infection. Acute myocardial infarction is the most common cause of death in healthy adults after total joint arthroplasty estimated at 0.25% and higher rates in patients with pulmonary disorders [22, 23]. The near three-fold increase in acute MI after primary TKA in patients with pulmonary HTN is notable. This highlights the need for perioperative specialized care with ICU access at a tertiary medical center. At our institution, we routinely utilize multiple perioperative interventions including minimal intraoperative narcotic use, continuous arterial blood pressure monitoring, gentle fluid resuscitation, liberal use of surgeon-directed periarticular anesthetics, and heavy emphasis on postoperative pulmonary hygiene combined with post-operative day 0 mobilization—all likely contribute to minimizing perioperative medical complications in these patients.
At 10 years, the cumulative incidences of revision and re-revision TKAs in this cohort were similar to rates reported in a healthy patient population and superior to other studies examining medically-complex populations undergoing TJA [24–29]. Additionally, clinical outcomes reliably increased for the cohort. Taken together, in the absence of medical complications, patients with pulmonary HTN who undergo primary or revision TKA can expect similar functional outcomes, as well as revision and reoperation rates to the general population.
We acknowledge the limitations to our study. First, the study is a retrospective review over an extended timeframe at a single tertiary care academic institution, potentially limiting its generalizability. Furthermore, as all our patients were extensively medically optimized prior to TKA, it is possible that this represents the best possible medical outcomes after primary and revision TKA. Specific documentation of cause of death outside of the perioperative period was inconsistent and we were unable to provide that data. Unfortunately, we did not capture the number of patients who were screened and deemed too high-risk for surgery. Finally, patient outcomes and complications were not stratified according to type or severity of pulmonary HTN which limits sub-cohort risk stratification.
In summary, this is the largest cohort of patients with pulmonary HTN undergoing contemporary primary and revision TKAs. Mortality risk was demonstrated to be higher than in the general population and when compared to patients without pulmonary HTN undergoing primary and revision TKA. Ninety-day mortality was 0.7% and 4.8% in primary and revision TKAs, respectively. However, there was a high incidence of perioperative medical complications, including death, at 6.5% in the primary TKA group and 14% in revision TKA group. In addition, the 10-year cumulative incidence of revision (with death as a competing risk) was 4.9% for primary TKAs and 16.1% for revision TKAs. There was a reliable improvement in clinical function. Patients with pulmonary hypertension should be medically optimized and closely managed in centers with immediate access to an ICU and a multi-disciplinary medical team.
Supplementary Material
Acknowledgement:
This work was in part funded by a grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) grant P30AR76312
Footnotes
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This investigation was performed at the Mayo Clinic, Rochester, MN
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