A 78-year-old male presented with a right femoral head fracture after recent fall. PMH included heart failure with reduced ejection fraction (EF 28%), COPD, hypertension, Type II DM, and chronic renal insufficiency. Outpatient medications included furosemide, quinapril, empagliflozin, and albuterol MDI. The patient was admitted and scheduled for right hemiarthroplasty. Preoperative vital signs, Hgb, platelets, and coagulation factors were all within normal limits. In the OR, spinal anesthesia was placed, and the patient was sedated with a propofol infusion. Shortly after injection of bone cement, the patient’s BP dropped to 85/50, HR 48, and end tidal CO2 was no longer detectable. Intravenous phenylephrine and ephedrine boluses were ineffective. Oxygen saturation dropped to 80%. Cardiac arrest ensued, and intubation and chest compressions were initiated. Epinephrine boluses were given. An emergently placed transesophageal echo (TEE) showed significant tricuspid regurgitation, a severely distended right ventricle, and interventricular septum shift with reduced LV volume. Epinephrine infusion was started. Spontaneous return of circulation was achieved with these interventions. Blood pressure normalized, and the surgery was completed. At the end of the procedure, the patient was noted to be responsive and following commands. The patient was extubated in the OR and transferred to ICU. The patient was discharged two days later with no neurological sequelae and negative cardiac workup for an ischemic event.


The case presented here is consistent with clinical manifestations of bone cement implantation syndrome (BCIS). In a 2009 British Journal of Anaesthesia article, A.J. Donaldson and colleagues proposed the following definition for BCIS: “Hypoxia, hypotension or both, and/or unexpected loss of consciousness occurring around the time of cementation, prosthesis insertion, reduction of the joint, or limb tourniquet deflation in a patient undergoing cemented bone surgery” (Br J Anaesth 2009;102:12-22). Additionally, they proposed the following severity classification:

  • Grade 1: moderate hypoxia (SpO2 <94%) or hypotension [fall in systolic blood pressure (SBP) >20%].
  • Grade 2: severe hypoxia (SpO2 <88%) or hypotension (fall in SBP >40%) or unexpected loss of consciousness.
  • Grade 3: cardiovascular collapse requiring CPR.

Although clinical presentation of Grades 2 and 3 BCIS are most likely seen intraoperatively, delayed clinical presentation may also be manifested up to 48-hours postoperatively. According to various case reports, these later presentations are often lower grade, exhibiting hypoxia and confusion in the PACU, or postsurgical inpatient hospitalizations (J Clin Orthop Trauma 2013;4:157-63).

The detrimental clinical effects of BCIS may also be long-lasting. In one 2021 retrospective study of 3,294 cemented arthroplasty patients, 30-day and three-year survival revealed overall lower survival rates in Grade 2 BCIS patients, 92% and 79%, respectively, and 0% 30-day survival in those with Grade 3 BCIS (Clin Orthop Relat Res 2021;479:755-63).

While most commonly associated with hip hemiarthroplasties, BCIS cases have been reported in many surgical procedures in which bone cement, a.k.a., polymethyl methacrylate (PMMA), is used, including hip, knee, and shoulder arthroplasties as well as vertebroplasties. According to the 2022 American Joint Replacement Registry (AJRR) annual report, approximately 790,000 total knee replacements and over 450,000 hip replacements are performed annually in the U.S., with 81.2% (641,480) and 5% (22,500) utilizing cemented fixation, respectively (asamonitor.pub/45frxlO).

One retrospective observational study of 3,294 various arthroplasty procedures revealed an overall BCIS incidence rate of 26% (Clin Orthop Relat Res 2021;479:755-63). Given the high relative frequency of this syndrome, increasingly large number of arthroplasties being performed, and increasingly older surgical population in the U.S., a review of the currently understood pathophysiology and anesthetic management of BCIS patients is presented here.

Although the pathogenesis and pathophysiology of BCIS are not yet fully established, several models have been proposed (Continuing Education in Anaesthesia Critical Care & Pain 2012;12:213-6). Results of several studies and clinical reports are consistent, citing right ventricular failure secondary to increased pulmonary artery pressure as the cause of systemic hypotension and sudden cardiac arrest (Anasthesiologie und Intensivmedizin 2019;60:124-33).

The earliest models to explain BCIS hypothesized that circulating PMMA monomers during surgery caused vasodilation and were responsible for some of the cardiovascular and pulmonary effects (J Clin Med 2023;12:2105). However, more recent studies suggest an embolic model, in which embolic debris such as fat, air, marrow, aggregates of fibrin, or cement particles cause mechanical obstruction of the pulmonary vasculature (J Clin Med 2023;12:2105).

In addition to these mechanical effects, there may also be chemical mediators such as proinflammatory and other vasoactive substances that are released as a result of the damage caused by these micro-emboli or released by the emboli themselves. Some of these mediators worsen pulmonary vasoconstriction while others act to decrease systemic vascular resistance (J Clin Med 2023;12:2105). Other chemical mediators that have been theorized to contribute to adverse hemodynamic effects of BCIS include histamine release and complement activation, as seen in anaphylactoid or hypersensitivity reactions (J Clin Med 2023;12:2105).

While several postmortem and echocardiographic studies in the literature support the embolic model, other subsequent studies have disputed the extent of microembolic debris alone accounting for all the features of BCIS. Instead, a combination of chemical mediators acting in conjunction with PMMA and embolic models may better explain the full clinical phenomena seen in BCIS (Br J Anaesth 2009;102:12-22; J Clin Med 2023;12:2105). Additionally, the patient’s underlying physiology and comorbidities, surgical technique, and the proposed surgery may also contribute to adverse reaction to bone cement (J Clin Med 2023;12:2105).

Given the proposed multimodal etiology of BCIS, strategies to prevent and manage BCIS are also multifaceted. Currently, no definitive consensus exists as to the preferred anesthetic technique to prevent complications from BCIS (Anesthesiology 2012;117:72-92; Cochrane Database Syst Rev 2016;2:CD000521). Prevention should therefore be aimed at identifying patients at highest risk for developing BCIS and optimizing their cardiovascular status preoperatively.

Risk factors associated with a higher incidence of BCIS include age >65, male sex, ASA Physical Status classification >3, severe cardiopulmonary disease, including pulmonary hypertension and COPD, as well as patients taking diuretics and coumadin preoperatively (J Clin Med 2023;12:2105). Other factors associated with increased risk include patients with osteoporosis, malignant tumors, pathologic fractures, intertrochanteric fractures, and long-stem arthroplasties (J Clin Med 2023;12:2105).

In these high-risk patients, additional intraoperative monitors, beyond the standard ones, may be implemented to detect subtle hemodynamic changes and guide corrective therapy if the need arises. These may include arterial lines, central lines, cardiac output monitors (invasive and non/semi-invasive), and transesophageal echocardiography (TEE). TEE may be especially useful to both diagnose BCIS by directly visualizing intracardiac emboli and right ventricular failure as well as to guide management to correct hemodynamic perturbations that accompany this syndrome.

Since right ventricular failure precipitated by pulmonary hypertension is thought to be the primary pathophysiological cause leading to hemodynamic compromise, the goals of managing unstable BCIS patients should be directed at reducing pulmonary vasoconstriction (inhaled nitric oxide and prostacyclin analogs, correct hypercarbia, hypoxemia, and acidosis), providing inotropic support (dobutamine and milrinone) to improve right ventricular contractility, and initiating volume resuscitation while avoiding fluid overload (J Clin Med 2023;12:2105).

Vasopressors with α1 agonist effects such as epinephrine, norepinephrine, and phenylephrine in the setting of severe hypotension may also be used judiciously to maintain right coronary perfusion (Continuing Education in Anaesthesia Critical Care & Pain 2007;7:89-94). Other proposed treatments have included serotonin antagonists (ondansetron), antihistamines (clemastine and cimetidine), anticholinergics (glycopyrrolate), and corticosteroids (J Clin Med 2023;12:2105).

Finally, several surgical factors have been shown to potentially reduce the risk of BCIS, including (Br J Anaesth 2009;102:12-22):

  • Achieving hemostasis before prosthesis insertion.
  • Use of a low-viscosity cement.
  • Pulse lavage of femoral canal prior to insertion of prosthesis.
  • Slow introduction of short-stem prosthesis.
  • Minimal pressurization of cement.
  • Use of suction catheter to depressurize intramedullary canal.
  • Drilling a venting hole in the femur prior to cement insertion.
  • Use a bone-vacuum cementing technique when mixing the cement.
  • Retrograde insertion of bone cement from distal to proximal.
  • Use of uncemented prosthesis in very high-risk patients.

Given these complex surgical and anesthetic factors, communication and collaborative management between the anesthesia, surgery, and relevant consultant services are vital to prevent and mitigate the complications that can arise from BCIS.

In the case presented, this patient possessed numerous high-risk criteria to develop BCIS, including advanced age, male sex, ASA Physical Status 3 status with severe cardiopulmonary disease/COPD, and preoperative diuretic usage. While advanced monitoring was not initially placed, a TEE placed after the patient suffered a full cardiac arrest confirmed a diagnosis of BCIS and helped guide fluid and vasopressor management.

Unfortunately, availability of TEE and the credentialed expertise to use it may not be present at all sites where BCIS may develop. Likewise, specific pulmonary vasodilators such as inhaled nitric oxide and intravenous prostacyclin analogs may also not be available when needed to treat severe BCIS. For these reasons, proper screening for high-risk candidates and discussion with the surgical team as to the surgical techniques that may best prevent the development of BCIS are highly recommended.

Finally, the reporter in this case did a commendable job rescuing this patient from a catastrophic event. Failure to rescue, defined as “the inability to prevent death after the development of a complication,” has garnered increasingly more attention as a quality and patient safety metric in the perioperative setting (asamonitor.pub/467D47T).

Anesthesiologists have been leaders in intraoperative crisis management and have promoted numerous human factors strategies such as emergency cognitive aids, simulation training, and crew resource management to improve failure-to-rescue measures (asamonitor.pub/467D47T).