Elevated Right Ventricular Systolic Pressure and Outcomes after Major Hip Surgery: A Case Control Study

doi:10.21203/rs.3.rs-4616819/v1

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Elevated Right Ventricular Systolic Pressure and Outcomes after Major Hip Surgery: A Case Control Study

https://doi.org/10.21203/rs.3.rs-4616819/v1

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Patients at risk of pulmonary hypertension (PH) frequently present for emergency orthopedic surgery. A right ventricular systolic pressure (RVSP) of 35 mmHg or above, calculated from a tricuspid regurgitant jet on transthoracic echocardiography (TTE) is widely considered an appropriate screening test for PH.¹ The aim of this study was to evaluate the impact of an elevated RVSP detected on preoperative TTE on outcomes after hip replacement or fracture fixation surgery. We undertook a retrospective, single centre, case control study of 115 adult patients who had a TTE before undergoing hip surgery over a six-year period.

Forty-eight patients (42%) had an elevated RVSP and 67 patients (58%) had a normal RVSP on preoperative TTE. Patients with an elevated RVSP were older and had a higher prevalence of atrial fibrillation and chronic obstructive pulmonary disease. In multivariate analysis there was no significant association between these variables and in hospital mortality. In keeping with the echocardiographic characteristics of high right-sided pressure, tricuspid regurgitation and right ventricular dilation occurred more frequently in the elevated RVSP group.

Patients with an elevated RVSP were significantly more likely to die in hospital, with all in hospital deaths occurring within this group (9/48 (19%) vs 0/67 (0%), p = < 0.001). Four patients died within one week of surgery after a cardiac arrest. The remaining 5 patients died a median of 26 (IQR 24–59) days after surgery due to pneumonia and progression of comorbid disease, often complicated by delirium.

This study highlights the potential association between an elevated preoperative RVSP and increased mortality after hip replacement or fracture fixation surgery.

Right Ventricular Systolic Pressure

Orthopedic Surgery

Outcomes

Pulmonary hypertension (PH) is a syndrome characterised by increased right ventricular afterload and subsequent progressive right ventricular (RV) dysfunction. Pulmonary hypertension is estimated to affect approximately 1% of the global population¹. The prevalence of PH is likely to increase as the population continues to age and as treatment for PH and its associated conditions improve. The number of patients with PH is also likely to increase following the revised hemodynamic definition, proposed at the 6th World Symposium on Pulmonary Hypertension, which reduced the mean pulmonary artery pressure (mPAP) threshold for the diagnosis of PH from 25mmHg to 20mmHg at rest, on right heart catheterization (RHC).² Studies have shown that mortality increases in patients with a mPAP above 19mmHg.³

Patients at risk of PH often present for emergency surgery in a hospital which is not a recognized PH centre. There may be insufficient time and limited access to advanced hemodynamic testing to establish a definitive diagnosis of PH. Anesthesia and surgery in patients with PH have an attendant risk of perioperative morbidity and mortality.⁴ The rate of major adverse cardiovascular events, including death was 8.3% in PH patients compared to 2% in non-PH patients after major non-cardiac surgery.⁵ The mortality rate increases to 15–50% for PH patients undergoing emergency surgery.⁶ Orthopedic procedures associated with perioperative bone marrow or cement embolization to the pulmonary circulation can also lead to acute right ventricular failure and death.⁷

A joint task force of the European Society of Cardiology and European Respiratory Society proposed that a peak velocity of tricuspid regurgitation of greater than 2.8 m/s on continuous wave doppler on transthoracic echo (TTE), which corresponds to a right ventricular systolic pressure (RVSP) of approximately 35mmHg, can be used as a screening test for PH. A subsequent RHC is required to establish a definitive diagnosis.¹

Recent literature has focused on the perioperative management of patients with an established diagnosis of PH.^4,6 These guidelines highlight the appropriate adjustment of pulmonary vasodilator therapy, optimizing the primary underlying conditions and identifying patients who should have their surgery undertaken in an expert PH centre.^4,6 There is a paucity of published evidence on the appropriate perioperative management of patients found to have an elevated RVSP on preoperative TTE but without a formal PH diagnosis.

The primary aim of this study was to compare the perioperative course and outcomes in patients with an elevated preoperative RVSP (≥ 35 mmHg) to those with a normal preoperative RVSP (< 35 mmHg), following hip fracture fixation or joint replacement surgery.

A retrospective, observational, case control study in a 719 bed, university-affiliated, teaching hospital was undertaken. The national PH service, the national Heart and Lung Transplantation service, the regional Major Trauma service and the national Extracorporeal Membrane Oxygenation service are based in our hospital. The study was approved by the Department of Anesthesia Audit Committee, a subgroup of the Mater Hospital Audit Committee, under The National Quality Improvement Directorate.

Medical records of all adult patients who underwent hip fracture fixation or joint replacement surgery over a six-year period from 30th September 2015 to 30th November 2021 were reviewed. The patient cohort included in this study were those presenting for emergency hip fracture repair and patients for elective joint replacement deemed too high-risk to have their surgery performed elsewhere. Patients scheduled for elective hip surgery and considered low-risk had their surgery performed in a sister hospital.

Data collected included patient demographics, functional status, past medical history, NT-pro-BNP plasma concentration and TTE results. TTE’s were performed by British Society of Echocardiography accredited echo-physiologists and all available data from the TTE reports was collected. We recorded the urgency for surgery, mode of anesthesia, whether invasive arterial blood pressure monitoring and central venous catheterization were utilised. The number of patients with hemodynamic instability (defined as one or more episodes when recorded mean arterial pressure was greater than 150 mmHg or less than 50mmHg) in the intra and postoperative period was noted. We recorded if the patient required admission to a critical care bed postoperatively, their critical care and hospital length of stay and their survival to hospital discharge.

Data was collected from IntelliSpace Critical Care and Anaesthesia software (Philips)^®, Centricity Software (GE HealthCare)^® and by retrospective chart reviews and transferred onto a Microsoft Excel spreadsheet. Statistical analysis was performed using MedCalc software (Belgium) ^® and GraphPad Prism version 10.0.0 for Windows (USA)^®. The Shapiro-Wilk test was used to test for normality of distribution. Non-parametric data was compared using the Mann Whitney U test and categorical variables were compared using the Chi square test. A two-tailed p value of less than 0.05 was set to indicate statistical significance for each test.

During the study period, 596 patients underwent hip surgery for joint replacement or fracture fixation in our hospital. Twenty-two patients were excluded as perioperative clinical notes were incomplete. Of the remaining 574 patients, 115 had a preoperative TTE and were included in the study population (Fig. 1).

TTE: transthoracic echocardiogram; RVSP: right ventricular systolic pressure

One hundred and fifteen of the 574 (20%) patients having hip surgery during the study period had a preoperative TTE. Of these 115 patients, 49 (42%) had a TTE ordered due to a history or clinical signs of congestive cardiac failure or structural heart disease, 32 patients (28%) had a TTE requested as part of a pre-operative assessment, 9 (8%) had a TTE to assess for infective endocarditis, 7 patients (6%) had a TTE requested due to a suspicion of acute coronary syndrome, 5 patients (4%) were requested as part of a falls work up and 5 patients (4%) had a TTE due to a history of pulmonary hypertension.

Forty-eight of the 115 patients (42%) who had a preoperative TTE were found to have an elevated RVSP and 67 patients (58%) had a normal RVSP. Twenty-nine patients (25%) had no recorded RVSP on their preoperative TTE due to insufficient tricuspid regurgitation or poorly visualised tricuspid valve, these patients were assigned to the normal RVSP group.

Five of the 115 patients (4%) had a previous diagnosis of pulmonary hypertension. All were found to have an elevated RVSP on TTE. Two had PH secondary to left heart disease and three had PH due to multifactorial mechanisms.

Table 1

Patient characteristics and comorbidities: elevated RVSP group versus normal RVSP group
	Elevated RVSP n = 48 (42%)	Normal RVSP n = 67 (58%)	P value
Baseline characteristics
Age, years, median, (IQR)	81 (74,89)	76 (65,84)	0.029
Male, no. (%)	19 (40%)	32 (48%)	0.396
ASA status
ASA class 4, no. (%)	11 (23%)	10 (15%)	0.276
Comorbidities
Cardiac disease
Heart failure, no. (%)	10 (20%)	6 (9%)	0.091
Ischemic heart disease, no (%)	21 (44%)	18 (27%)	0.059
Valve replacement, no. (%)	3 (6%)	4 (6%)	1.000
Atrial fibrillation, no. (%)	22 (46%)	13 (19%)	0.002
Pulmonary hypertension, no. (%)	5 (10%)	0 (0%)	N/A
Respiratory disease
COPD, no. (%)	14 (29%)	9 (13%)	0.034
Smoking, no. (%)	9 (19%)	8 (12%)	0.300
Obstructive sleep apnea, no. (%)	2 (4%)	3 (4%)	1.000
Asthma, no. (%)	3 (6%)	3 (4%)	0.623
Bronchiectasis, no. (%)	3 (6%)	3 (4%)	0.623
Vascular disease
Hypertension, no. (%)	24 (50%)	33 (49%)	0.916
Cerebrovascular disease / Transient ischemic attack, mo. (%)	8 (16%)	13 (19%)	0.679
Peripheral vascular disease / venous ulcers, no. (%)	1 (2%)	8 (12%)	0.050
Abdominal aortic aneurysm, no. (%)	4 (8%)	5 (7%)
Thromboembolic disease
Deep vein thrombosis / pulmonary embolism, no. (%)	4 (8%)	7 (10%)	0.715
Renal disease
Chronic kidney disease, no. (%)	10 (20%)	10 (14%)	0.394
Dialysis dependence, no. (%)	1 (2%)	2 (3%)	0.739
NT Pro BNP
NT-pro BNP, ng/L (median, IQR)	637 (531,1779)	882 (390,7625)	0.620

RVSP: right ventricular systolic pressure; ASA: American Society of Anesthesiology; COPD: Chronic obstructive pulmonary disease; NT-proBNP: N-terminal pro b-type naturetic peptide; IQR: interquartile range.

In univariate analysis, patients with an elevated RVSP were older (81 vs 76 years) but the number of patients with an American Society of Anesthesiology (ASA) class of 4 or above in both groups were similar (23% vs 15%) (Table 1). The prevalence of vascular disease thromboembolic and renal disease was similar in both groups (Table 1). The number of patients with atrial fibrillation and chronic obstructive pulmonary disease was higher in the elevated RVSP group (Table 1). A preliminary multivariate analysis showed there were no statistically significant associations between age (OR 0.95, 95% CI 0.8767 to 1.029), atrial fibrillation (OR 0.93, 95% CI 0.1786 to 5.142), or chronic obstructive pulmonary disease (OR 0.28, 95% CI 0.03217 to 2.120) and in-hospital mortality between the elevated versus normal RVSP groups.

Patients with an elevated RVSP were more likely to have mixed valvular heart disease, although overall prevalence was low. In keeping with the echocardiographic characteristics of high right-sided pressure, tricuspid regurgitation and right ventricular dilation occurred more frequently in the elevated RVSP group. There was no significant difference in left-sided valvular pathologies on TTE. There was no significant difference in left or right ventricular function between the groups. (Table 2)

Table 2

TTE results: elevated RVSP group versus normal RVSP group.
	Elevated RVSP n = 48 (42%)	Normal RVSP n = 67 (58%)	P value
Left ventricular pathologies
Left ventricular dysfunction (EF ≤ 40%), no. (%)	6 (12%)	6 (9%)	0.602
Left ventricular hypertrophy, no. (%)	8 (17%)	6 (9%)	0.200
Right ventricular pathologies
Right ventricle function reduced, no. (%)	4 (8%)	2 (3%)	0.230
Tricuspid Annular Plane Systolic Excursion, cm (median, IQR)	2 (2, 2)	2 (2, 2)	0.185
Valvular pathologies
Moderate to severe left sided valvular pathology (Mitral or aortic valve disease), no. (%)	8 (17%)	6 (9%)	0.200
Tricuspid regurgitation, no. (%)	16 (33%)	1 (1%)	< 0.0001
Pulmonary regurgitation, no. (%)	0 (0%)	1 (1%)	0.489
Multiple valvular pathologies, no. (%)	3 (6%)	0 (0%)	0.043
Echogenic parameters associated with Pulmonary Hypertension
RVSP mmHg (mean, standard deviation)	47 ± 10	24 ± 7	< 0.0001
IVC dilated, no. (%)	4 (8%)	2 (3%)	0.127
Right ventricular dilation, no. (%)	8 (17%)	2 (3%)	0.009
RVSP: right ventricular systolic pressure; EF: ejection fraction; IVC: inferior vena cava;

IQR: interquartile range.

Ninety-eight (85%) patients in our study underwent emergency surgery. Seventy-four patients (64%) had hip hemiarthroplasty surgery, 40 patients (35%) underwent either total or revision arthroplasty and one patient (1%) had a closed reduction of a fractured femur.

Table 3

Perioperative course and outcome: elevated RVSP group versus normal RVSP group.
	Elevated RVSP n = 48 (42%)	Normal RVSP n = 67 (58%)	P value
Surgery
Emergency surgery, no. (%)	42 (87%)	56 (84%)	0.656
Duration of surgery: minutes, (median, IQR)	90 (60,105)	90 (60,120)	0.043
Hemiarthroplasty of femur, no. (%)	37 (77%)	37 (55%)	0.015
Total or revision arthroplasty, no. (%)	10 (20%)	30 (45%)	0.005
Anesthesia
Spinal anesthesia, no. (%)	26 (54%)	40 (60%)	0.455
General anesthesia, no. (%)	22 (45%)	27 (40%)	0.748
Arterial line inserted, no. (%)	33 (69%)	39 (58%)	0.231
Central venous catheter inserted, no. (%)	11 (23%)	12 (18%)	0.511
Vasopressor infusion via CVC, no. (%)	7 (15%)	7 (10%)	0.419
Hemodynamic instability, no. (%)	17 (35%)	14 (21%)	0.096
Outcome
Admitted to a Critical Care bed, no. (%)	8 (17%)	11 (16%)	0.887
Critical Care LOS, days, (median, IQR)	2 (2, 3)	3 (3, 4)	0.190
Time from surgery to hospital discharge, days (median, IQR)	16 (7, 29)	14 (8, 28)	0.878
Hospital mortality, no. (%)	9 (19%)	0	< 0.001
Time to death after surgery, days, (median IQR)	22 (6,26)	N/A	N/A
Deaths ≤ 7 days after surgery, no. (%)	4 (44%)	N/A	N/A
Deaths ≥ 8 days after surgery, no. (%)	5 (55%)	N/A	N/A
Cause of death: cardiac arrest, no. (%)	4 (44%)	N/A	N/A
Cause of death: pneumonia ± progression of comorbid conditions, no. (%)	5 (55%)	N/A	N/A
RVSP: right ventricular systolic pressure; CVC: central venous catheter;

Hemodynamic Instability: number of patients with intra- or postoperative mean arterial blood pressure > 150 or < 50 mmHg; LOS: length of stay; IQR: interquartile range.

The mode of anesthesia, duration of surgery perioperative monitoring, frequency of perioperative hemodynamic instability and postoperative care destination did not differ significantly between the groups (Table 3). There was no difference in the median time from surgery to hospital discharge in both groups (16 versus 14 days).

Patients with an elevated RVSP were significantly more likely to die in hospital, with all inpatient deaths occurring within this group (9/48 (19%) vs 0/67 (0%), p = < 0.001) (Table 3). Of the 9 patients who died in hospital, the median age was 82 years, the average ASA classification was 4 and the mean RVSP was 48 mmHg. One of the patients who died prior hospital discharge had a definitive diagnosis of PH, the remaining 8 patients had no previous diagnosis of PH. Eight of the 9 patients who died underwent emergency surgery. Five of the 9 patients who died had general anesthesia, the remaining patients had spinal anesthesia. Five of the patients who died had a central venous catheter placed, required vasopressors and had one or more episodes of hemodynamic instability. All of the patients who died had an arterial line placed perioperatively. Only 2 of the 9 patients who died were admitted to a Critical Care bed postoperatively.

Four of the patients died within one week of surgery after a cardiac arrest. The remaining 5 patients died a median of 26 (IQR 24–59) days after surgery due to pneumonia and progression of comorbid disease, often complicated by delirium. During the study period, the mortality rate for all patients undergoing hip surgery (n = 574) was 4 percent.

The prevalence of PH in the global population is estimated to be 1% and rising up to 10% in those aged 65 years or above.⁸ Patients are living longer with PH due to advancements in therapies and as a result, the number of PH patients requiring emergent surgery continues to increase.⁶

TTE is not routinely indicated in all patients undergoing hip surgery. However, a preoperative echocardiogram should be considered if there is a history of significant cardiac disease or if the patient has new signs or symptoms suggestive of heart failure.⁹

It is widely accepted that a peak velocity of tricuspid regurgitation > 2.8m/s on TTE (calculated with right atrial pressure), corresponds to an RVSP of approximately 35mmHg and can be used to determine the probability of PH.^1,9 In a recent epidemiological study, patients with a RVSP of 33–39 mmHg were noted to have an increased mortality compared to patients with RVSP < 33 mmHg.¹⁰ Echocardiographic estimates of RVSP are subject to potential inaccuracies in patients with suboptimal windows.³ Hence additional variables, such as interventricular septal flattening, right atrial area, inferior vena cava diameter and respiratory variation and diameter of the pulmonary artery, are used to refine the echocardiographic probability of PH.¹

In our study, 48 of 115 patients (42%) had an elevated RVSP, one of the echocardiographic features suggestive of PH. Only 5 of these patients (4%) had a previous diagnosis of PH. This suggests that there is a significant number of patients with elevated RVSP in the community, who may be at risk of PH but remain undiagnosed and untreated in the community.

One hundred and fourteen of the 115 patients (99%) had either a total or hemiarthroplasty of the hip, with 85% of patients having emergency surgery. (Table 3) Total hip replacement is traditionally associated with a longer duration of surgery when compared to hip hemiarthroplasty.¹¹ Patients undergoing total hip replacement with an established diagnosis of PH have an approximately 4-fold increased adjusted risk of mortality compared to patients without PH.¹² A higher proportion of patients in the elevated RVSP in our study group underwent hemiarthroplasty of the hip however the duration of surgery was similar in both groups.

We found no difference in perioperative management (mode of anesthesia, intraoperative monitoring, incidence of hemodynamic instability or admission to a Critical Care bed) between the two groups of patients. Sixteen percent of all our patients were admitted to a Critical Care bed after surgery. In a study from Edinburgh, 2.4% of elderly patients who presented with hip fracture required admission to the Critical Care unit.¹³

The time from surgery to hospital discharge was prolonged in both groups (16 versus 14 days) reflecting the general frailty and burden of comorbid disease encountered in this cohort of patients presenting for emergency hip surgery. Delays in discharge are contributed to by a multitude of factors, including inadequate stepdown and community care.¹⁴

In our study, nine patients died before hospital discharge. All of the deaths were recorded in the elevated RVSP patient group with no deaths in the normal RVSP group (9/48 (19%) vs 0/67 (0%), p = < 0.001). Four patients died within one week of surgery after a cardiac arrest. The remaining 5 patients died a median of 26 (IQR 24,59) days after surgery due to pneumonia and progression of comorbid disease, often complicated by delirium. These findings suggest that identifying elevated RVSP preoperatively could improve risk assessment with allocation of appropriate postoperative resources and follow-up for these patients.

Patients with elevated preoperative RVSP were older and had a higher incidence of atrial fibrillation and chronic obstructive pulmonary disease. Despite the low event rate of in-hospital mortality in our study population, a multivariate analysis did not establish an additional mortality risk with these possible confounding factors. Similarly in a study of 47,784 patients referred for echocardiography, even a mild elevation of RVSP was found to be pathogenic in its own right and the associated increased mortality was not explained fully by comorbid conditions.¹⁰

Ming et al. reviewed 25 patients with a definitive diagnosis of PH who underwent elective hip or knee replacement surgery in a recognized PH centre.¹⁵ They reported no perioperative deaths, however 11 patients (44%) experienced a significant complication, including hypotension requiring vasopressors, blood transfusion and non-orthopedic infection. The authors concluded that with careful patient selection and optimal perioperative care, good outcomes can be achieved. ¹⁵ In a similar study of 16 patients with severe PH undergoing major orthopedic surgery, one patient (6%) died due to pneumonia and 6 patients (37%) had significant postoperative complications including bleeding, dysrhythmia and poor wound healing.¹⁶

The mortality rate in our patients was higher than in the above studies despite their patients having a definitive diagnosis of PH, with many already stabilised on PH therapy and were undergoing elective procedures in an established PH centre. Under these circumstances, a comprehensive preoperative assessment by a multidisciplinary team can formulate an individualized perioperative care plan. In contrast, the majority of patients in our study were undergoing emergency surgery or were deemed high risk with only 4% having a definitive diagnosis of PH. Current guidelines recommend surgery within 36 hours for patients with hip fracture, limiting the time available for preoperative optimization.^4,17

Our study has several important limitations. Our retrospective observational study, can only infer association and not causation. The multivariate analysis performed is limited by the low event rate of in hospital mortality within our study. The patients included our study were high risk including those presenting for emergency hip fracture repair and patients for elective joint replacement deemed too high risk to be performed elsewhere. Only 115 out of a total of these 574 (20%) patients having hip surgery during the study period had a preoperative TTE, with the decision to request a preoperative TTE likely including patients considered at even higher perioperative risk. Our elevated RVSP patient cohort had some echocardiographic features of PH, however without RHC data, no definitive diagnosis of PH can be made. The preoperative TTE’s performed on our patients were not focused right-heart studies, additional features used to refine the echogenic probability of pulmonary hypertension were not consistently included in the TTE reports. Our study was conducted in a single hospital that has a well-established PH service, thus the findings may have limited generalisability. Other than documenting hospital length of stay and mortality, our study did not include ward-based follow-up of our patients.

In conclusion, 42% of patients presenting for emergency hip surgery or deemed high-risk for elective hip surgery were noted to have elevated RVSP on preoperative TTE. Patients with an elevated RVSP were older with a higher incidence of chronic obstructive airway disease and atrial fibrillation. In multivariate analysis there was no significant association between these variables and in hospital mortality. Those found to have an elevated RVSP were significantly more likely to die in hospital with all in hospital deaths occurring within this group. Just under half of the deaths occurred within one week of surgery after a cardiac arrest. The remainder of the deaths occurred a median of 26 (IQR 24–59) days after surgery and were due to pneumonia and progression of comorbid disease.

These results highlight the importance of acquiring high quality preoperative TTE examinations when indicated. Due attention should be given to the finding of RVSP elevation, additional variables used to clarify the echocardiographic probability of PH should be sought including interventricular septal flattening, right atrial area, inferior vena cava diameter and respiratory variation and diameter of pulmonary artery.

The results also suggest that detecting an elevated RVSP preoperatively may allow risk stratification and facilitate open discussion with the patient and their caregiver. Allocation of the necessary resources for follow-up care, particularly in the first week after surgery, could reduce mortality in this patient cohort. A future prospective study would be beneficial to examine the outcomes after hip surgery in patient with an elevated preoperative RVSP compared to patients with a normal RVSP with both groups well matched for age and comorbid conditions. A trial to examine the impact of early postoperative interventions such as heart failure management, treatment of nosocomial infections and mobilisation in patients with elevated RVSP identified on preoperative TTE would also be useful.

Conflict of interest

The authors declare no conflict of interest

Ethical approval

The study was approved by the Department of Anesthesia Audit Committee, a subgroup of the Mater Hospital Audit Committee, under The National Quality Improvement Directorate

Funding

No funding was provided for this study.

Author Contribution

MC: Initial concept of project, data acquisition, data analysis, composition of first and final draft, DOD: data analysis, critical review, final approval of version to be published, BM: critical review, final approval of version to be published, SG: critical review, final approval of the version to be published, AM: concept and study design, critical review, final approval of version to be published.

Acknowledgement

We acknowledge D. Murray (Health Records Department, Mater Hospital Dublin) for assistance with medical records. We also acknowledge C. Quinn, M. O’ Reilly, S. Joseph and M. Josy (Clinical Audit Nurse Specialists, Mater Hospital Dublin) for their assistance with data acquisition.

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No competing interests reported.

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Elevated Right Ventricular Systolic Pressure and Outcomes after Major Hip Surgery: A Case Control Study

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