Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5851_Библиотеки_им_академика_М_И_Перельмана.pdf
cute Pulmonary Embolism
8
A
Table 8.9 (continued)
Medication Route Dose
Direct thrombin inhibitors
Argatroban IV 2mcg/kg/min
Bivalirudin IV 0.15–0.2mg/
*
Additional dosing considerations are described in Table8.10
aPTT activated partial thromboplastin time, CrCl creatinine clearance, HIT heparin-induced
thrombocytopenia, IV intravenous, PE pulmonary embolism, SC subcutaneous, UFH unfractionated heparin
0.25–1.5mcg/
kg/min if
critically ill,
hepatic
dysfunction, or
heart failure
kg/h or
CrCl <60mL/
min:
0.04–0.08mg/
kg/h
Dosing Weight
Considerations
Use actual
body weight
Use actual
body weight
Dose
Adjustment Consideration
Titrate to
therapeutic
aPTT (1.5–3
times control)
according to
institutional
protocol
Titrate to
therapeutic
aPTT (1.5–2.5
times control)
according to
institutional
protocol
Commonly reserved
for patients with
heparin-induced
thrombocytopenia
or heparin
resistance
Commonly reserved
for patients with
heparin-induced
thrombocytopenia
or heparin
resistance
191
8.3.2 High-Risk PE
High-risk PE is classically dened with the presence of hemodynamic instability or
cardiac arrest. Patients can present with persistent hypotension (systolic BP
<90mmHg or drop ≥40mmHg lasting longer than 15min) or obstructive shock
requiring vasopressor support despite adequate lling status and end-organ hypoperfusion [59]. It is important to distinguish the cause of hemodynamic instability
in PE since other critical illnesses can present similarly, such as new-onset arrhythmia, hypovolemia, or sepsis. Patients with high-risk PE will require immediate
interventions, such as hemodynamic support or reperfusion therapy, in addition to
anticoagulation. Given the patient’s critical illness and the potential for additional
interventions, a parenteral anticoagulant with a quick onset and offset of action is
preferred. UFH is typically the agent of choice in patients without contraindications
to heparinoids, with the same factor Xa inhibition targets regardless of whether
thrombolysis is administered [72]. There are studies that have utilized LMWH
safely in the setting of thrombolysis [54, 92]. However, it may be prudent to consider the patient’s increased risk of bleeding as well as the need for quick reversal
pending invasive procedures, especially with the advent of advanced endovascular
therapies for PE.
The emergent use of thrombolytics and/or interventional procedures is described
in the forthcoming sections.
Supportive care is crucial for patients with high-risk PE who present with hypoxemia, shock, or acute RV failure. Supplemental oxygen should be administered to
patients with SaO
<90%. In patients who are refractory to conventional oxygen
2
192
S. K. Kim and L. A. Igneri
supplementation, high-ow oxygen or mechanical ventilation (invasive or noninvasive) may be considered. Intubation should be proceeded with caution, as RV dysfunction predisposes patients to severe decompensation with anesthesia and
positive-pressure ventilation [59]. Optimal induction agents should minimize the
incidence of hypotension. When providing mechanical ventilation, the 2019 ESC
guidelines recommend 6mL/kg of tidal volume and end-inspiratory plateau pressure <30cm H2O [59].
In patients with acute RV failure associated with PE, CO and volume status should
be closely monitored. Cautious use of intravenous crystalloids administered at low
volumes ≤500mL can help identify patients with low CO that are preload dependent.
Patients with a normal or low central venous pressure (CVP) may particularly benet
from volume optimization. However, aggressive volume administration may have a
paradoxical effect of decreasing CO by over-distending the RV.Vasoactive medications such as norepinephrine or dobutamine are often utilized to support reduced
perfusion. Norepinephrine, a mixed alpha/beta1-adrenergic receptor agonist, increases
systemic blood pressure but may lead to worsened tissue perfusion due to excessive
vasoconstriction. An inotropic agent such as dobutamine can increase CO but may
worsen hypotension requiring additional vasopressor support [59]. Vasodilator therapy may decrease PAP and PVR; however, it also decreases systemic blood pressure
when given intravenously. The efcacy of inhaled vasodilators such as nitric oxide or
prostacyclins is limited in the context of RV dysfunction from acute PE.
At centers that provide mechanical circulatory support (MCS), the temporary use
of venoarterial extracorporeal membrane oxygenation (VA-ECMO) may be helpful
in stabilizing a patient with high-risk PE. However, ECMO may predispose the
patient to additional harm, including increased risk for bleeding or infection. Patient
outcomes vary depending on the clinician expertise and experience. In patients with
cardiac arrest associated with acute PE, advanced life support guidelines are followed, with an early consideration for thrombolytic therapy [59].
8.3.3 Denitive Anticoagulation Duration
The duration of anticoagulation post-PE depends on patient-specic factors, provoking events, and risk of recurrence (Table8.10). All patients with PE should be
treated with anticoagulation for a minimum of 3months, with an option to extend to
6months. In certain cases, indenite anticoagulation may be warranted. The decision for anticoagulation duration will require a careful assessment of risk factors.
Patients who have an identiable, major transient risk factor that is reversible have
a lower risk of VTE recurrence and can discontinue therapy after 3months. On the
other hand, patients without any identiable risk factors, or patients with active
cancer, recurrent VTE, or antiphospholipid antibody syndrome, may warrant lifelong anticoagulation [59]. In patients who are eligible for extended anticoagulation
without cancer receiving DOACs, a reduced dose of apixaban or rivaroxaban can be
considered after the rst 6months of therapy.
8 Acute Pulmonary Embolism
Table 8.10 Duration of denitive anticoagulation [25]
Persistent risk factor Prior VTE
No identied persistent
risk factor
Cancer – – Recommend indenite or
Antiphospholipid
antibody syndrome
Other persistent risk
factor
First episode
of PE
Recurrent PE No major risk factor
– – Recommend indenite
– – Consider indenite beyond
Presence of Transient/
Reversible Risk factor Duration of anticoagulation
Major risk factor present Discontinue after 3months
Minor risk factor
present
No identiable risk
factor present
present
Consider indenite beyond
3months
Consider indenite beyond
3months
Recommend indenite
beyond 3months
until cancer is cured
beyond 3months
3months
193
8.4 Systemic Thrombolytic Therapy
Due to the risk of bleeding with systemic thrombolytic therapy, it should be reserved
for use in patients with PE that present with high-risk features, including hypotension (e.g., SBP <90mmHg or a drop of 40mm Hg or more for more than 15minutes), bradycardia, or pulselessness [59, 77, 99]. It may be considered for those with
intermediate PE whose clinical course suggests imminent progression to hemodynamic decompensation after starting anticoagulation provided that the risk for
bleeding remains low.
8.4.1 Evidence forSystemic Thrombolysis inPE
8.4.1.1 High-Risk PE
Thrombolysis in high-risk PE is based on low-level evidence evaluating the use of
alteplase, streptokinase, urokinase, reteplase, and desmoteplase in this population
[59, 77, 99].
The only prospective study of thrombolytics in high-risk PE randomized eight
patients with PE-associated cardiogenic shock to receive 1,500,000IU streptokinase IV over 1hour and heparin 10,000units IV bolus followed by infusion or heparin alone. The trial was stopped early after all four patients in the heparin-only
group died within 3hours of randomization compared to zero in the thrombolytic/
heparin group, p=0.02 [44]. Although there were signicant limitations with this
study, including small sample size and difference in time from PE onset to randomization (2.5hours in the streptokinase plus heparin group versus 34.75hours in the
heparin-only group), time to onset of shock was similar between groups. Ultimately,
194
S. K. Kim and L. A. Igneri
right ventricular myocardial infarction and massive PE were identied on autopsy
in the heparin-only group, suggesting that the prompt administration of thrombolytic therapy was responsible for improving outcomes in the thrombolytic/heparin
group [44].
Thereafter, studies describing outcomes of patients who received thrombolysis in
high-risk PE are largely registry based. In ICOPER, 4.2% of patients with conrmed PE presented with hemodynamic instability, and 13% were treated with
thrombolysis. The adjusted mortality rate in hemodynamically unstable patients
was 58.3%. Major bleeding occurred in 10.5% of the cohort and was noted to be
more common in patients that received thrombolytic therapy [35]. RIETE was an
international, multicenter, prospective registry study of 15,520 patients with acute
VTE that found that patients with acute, symptomatic, high-risk PE had an OR 16.3
(95% CI, 8.50–31.4) of developing a fatal PE [63]. Out of the overall cohort, 1.2%
received thrombolytic therapy, but no bleeding outcomes were described [63].
The EMPEROR study was a prospective, multicenter, observational registry
describing the diagnosis, treatment, and outcomes of patients presenting to the ED
with acute PE [84]. PE was conrmed in 1880 patients, with 33 receiving alteplase
(n=29) or tenecteplase (n=4) in the ED and 12 receiving alteplase after hospital
admission. Among the patients receiving thrombolytics in the ED, only 9.1% met
the denition of high-risk PE (e.g., hypotension on presentation). Of the 20 patients
with conrmed PE that died, 12 presented with at least one high-risk feature (e.g.,
SBP <90mmHg, elevated troponin, or RV hypokinesis), but only 3 patients received
thrombolytics. In patients that received thrombolysis, no deaths were attributable to
bleeding complications [84].
Due to the increased risk of death seen when thrombolytics are withheld or
delayed in high-risk PE, it would be unethical to perform a future randomized, controlled trial comparing modern thrombolytic therapies (e.g., alteplase or tenecteplase)
with anticoagulation to anticoagulation alone. Therefore, outcomes following the
administration of these thrombolytics in patients with high-risk PE are described in
case reports and cohort studies only [13, 94].
Despite the low-quality evidence, guidelines recommend the use of brinspecic,
second- and third-generation thrombolytics (alteplase and tenecteplase,
respectively) over rst-generation, non-brin-specic thrombolytics (streptokinase
and urokinase) due to their more favorable administration and pharmacokinetic proles [59, 77, 99]. Table8.11 describes the dosing and pharmacokinetic considerations of thrombolytic therapy for PE.
Intermediate-Risk PE
8.4.1.2
Routine use of reperfusion therapy with systemic thrombolytics is not recommended in all intermediate-risk PE because of the high risk for bleeding complications. However, select patients with intermediate-risk PE may benet provided that
the risk for bleeding complications does not outweigh the potential benets gained
from thrombolysis.
Acute Pulmonary Embolism
8
Table 8.11 Dosing and pharmacokinetic considerations of thrombolytic therapy for PE
Dosing studied in PE
Thrombolytic High risk Intermediate risk Cardiac arrest Half-life
Alteplase 100mg IV infusion
Tenecteplase – Weight-based IV push.
Streptokinase 250,000units IV
*
May opt to administer alteplase 100mg dose as 10mg IV bolus followed by 90 mg over 2h;
50mg dose as 10mg IV bolus followed by 40mg over 2h
*
over 2h
loading dose infused
over 15–30min then
100,000units/h for
12–24h
100mg IV over 2h
50mg IV over 2h
0.5mg/kg (patients
less than 50kg) over
2h
0.6mg/kg over 2h
<60kg: 30mg
≥60–<70kg: 35mg
≥70–<80kg: 40mg
≥80–<90kg: 45mg
≥90kg: 50mg
1.5million units IV
infusion over 2h
250,000units IV
loading dose infused
over 15–30min then
100,000units/h for
12–24h
*
50mg IV push
*
over 1min
(may repeat
after 15min of
CPR)
50mg IV
infusion over
15min
(continue CPR
for 15min)
Weight-based
IV push.
<60kg:
30mg
≥60–<70kg:
35mg
≥70–<80kg:
40mg
≥80–<90kg:
45mg
≥90kg:
50mg
– 18min
5min
Initial:
20–24min
Terminal:
90–130min
195
The pharmacist clinician can assist in identifying patients with intermediatehigh- risk PE who are at imminent risk of developing hemodynamic collapse, where
systemic thrombolytic therapy may be considered:
• Presence of RV dysfunction
• Troponin elevations
• sPESI ≥1
• Lactate of ≥2mmol/L
• Conrmed concomitant DVT
• BNP elevations
• Shock index (heart rate/systolic BP) >1 [39, 59, 77, 99]
Much controversy exists surrounding the choice of systemic thrombolytic therapy,
dosing strategy, and timing of administration in intermediate-risk PE.Select, pivotal
studies evaluating thrombolytic therapy in intermediate-risk PE are reviewed herein.
196
S. K. Kim and L. A. Igneri
The largest prospective study evaluating alteplase for intermediate-risk PE randomized 256 patients with RVD on echocardiogram or RV strain on ECG to
alteplase 100 mg versus placebo in addition to heparin [56]. Signicantly more
patients met the composite endpoint of in-hospital mortality or need for treatment
escalation in the placebo versus alteplase groups (24.6% versus 11%, p=0.006),
which was driven by the need for treatment of hypotension, use of rescue thrombolysis, intubation, CPR, surgical embolectomy, or catheter-based intervention.
Mortality was not statistically signicant between the alteplase and placebo groups
(3.4% versus 2.2%, p=0.71), and there were no differences in major or fatal bleeding [56].
MOPETT was a prospective, open-label study evaluating a “safe dose” of
alteplase in PE.One hundred twenty-one patients with symptomatic PE in ≥2 lobes
were randomized to either alteplase 50mg (patients <50 kg received 0.5mg/kg)
with anticoagulation or anticoagulation alone. Alteplase signicantly reduced the
incidence of pulmonary hypertension or recurrent PE at 28months (16% versus
63%, p<0.001), and no bleeding events occurred in either group [92]. Notably, the
incidence of pulmonary hypertension was higher compared to prior literature, and
nearly 80% of patients in the alteplase group received enoxaparin 1mg/kg (maximum 80mg) every 12hours, which differs from other thrombolytic studies utilizing
heparin as the main anticoagulant. Importantly, RVD was not a requirement for
inclusion potentially indicating a less critically ill patient population than in the
previous Konstantinides study [56].
Due to the lack of clear evidence to support one alteplase dosing strategy over
another for PE, there is widespread use of either 50mg (“half-dose”) or 100mg
(“full-dose”) depending on clinician assessment of an individual’s risk for decompensation versus benet. A retrospective cohort study including data from 3768
patients across 420 hospitals in the Premier Healthcare Database compared outcomes in patients receiving 50mg versus 100mg alteplase for PE.There was no
difference in hospital mortality (13% versus 15%, p= 0.3), cerebral hemorrhage
(0.5% versus 0.4%, p = 0.67), gastrointestinal bleeding (1.6% versus 1.6%,
p=0.99), acute blood loss anemia (6.9% versus 4.6%, p= 0.11), or documented
brinolytic adverse events (2.6% versus 2.8%, p=0.82) with half-dose versus fulldose alteplase [
53]. However, patients receiving half-dose alteplase represented a
less critically ill population as they were less likely to require vasopressor therapy
(23.3% versus 39.4%, p<0.01) and invasive ventilation (14.3% vs. 28.5%, p<0.01)
at baseline compared to patients receiving full-dose, which is likely a result of clinician selection bias. A propensity-matched analysis found that half-dose alteplase
was associated with increased treatment escalation (53.8% versus 41.4%, p<0.01)
due to the need for secondary thrombolysis (25.9% versus 7.3%, p<0.01) and catheter thrombus fragmentation (14.2% vs. 3.8%, p<0.01), as well as a higher median
cost of care ($103,843 versus $76,495 p<0.01) [53].
PEITHO is the largest study of thrombolytic therapy in intermediate-risk
PE.This international, multicenter, double-blinded trial randomized 1006 patients
with PE complicated by RVD and elevated troponin (intermediate-high risk based
on current PE classication) to either weight-based tenecteplase or placebo in
8 Acute Pulmonary Embolism
197
combination with heparin. Tenecteplase was associated with a signicant reduction
in death or hemodynamic compromise at day 7 (OR 0.44; 95% CI, 0.23–0.87;
p=0.02). However, hemodynamics drove the difference in the primary outcome as
there was no difference in death within 7 and 30days. Unfortunately, compared to
placebo, tenecteplase increased major extracranial bleeding at 7 days (OR 5.55;
95% CI, 2.3–13.39; p < 0.001) and stroke (OR 12.10; 95% CI, 1.57–93.39;
p=0.003), with ten hemorrhagic strokes occurring in the tenecteplase group compared to one in the placebo group [72]. Additionally, no difference in long-term
survival, dyspnea, functional limitation, residual pulmonary hypertension, RVD, or
CTEPH was seen in a 24-month outcome follow-up in 709 of the original patients
in the PEITHO study [58]. These ndings suggest that the benet of systemic
thrombolysis in patients with intermediate-high-risk PE may be countered by the
increased risk of major bleeding. At this time, it is unknown whether alternative,
lower dose tenecteplase strategies may have a more favorable risk-benet ratio in
intermediate-risk PE, similar to recent ischemic stroke literature.
Systemic thrombolytics should be reserved for patients with intermediate-highrisk PE at imminent risk for progression to hemodynamic collapse. The pharmacist
clinician must be familiar with the nuances, strengths, and limitations of guideline
recommendations and primary literature surrounding thrombolytic dosing in PE
and be prepared to collaborate with the critical care team to develop individualized
care plans.
8.4.1.3 Cardiac Arrest
It is estimated that 2–10% of cardiac arrests are attributable to suspected or conrmed PE [29]. Use of thrombolytic therapy in conjunction with standard ACLS
resuscitation pathways has been proposed to resolve both coronary and pulmonary
thromboses. Current cardiopulmonary resuscitation guidelines recommend adjunctive thrombolytic therapy, surgical embolectomy, and mechanical embolectomy as
emergency treatment options when PE is the conrmed cause of cardiac arrest and
suggest thrombolysis be considered when PE is the suspected cause of cardiac
arrest [78].
A double-blind, prospective study randomized 233 patients to receive either
alteplase 100mg IV over 15minutes or placebo if unresponsive to one minute of
standard ACLS therapy for out-of-hospital cardiac arrest (OHCA) with pulseless
electrical activity [1]. No signicant difference was seen in survival to hospital discharge in the alteplase (0.9%) versus placebo (0%) groups (p=0.99) or in any secondary endpoint including the return of spontaneous circulation (ROSC), hospital
LOS, hemorrhage, or neurologic outcomes [1]. The low rate of survival in either
group as well as the low number of patients with conrmed PE may have contributed to the inability to show a difference between interventions.
Another double-blind, multicenter trial done in Europe randomized 1050
patients with witnessed OHCA to either weight-based tenecteplase or placebo as
an adjunct to prehospital CPR, but was ultimately terminated early due to interim
198
S. K. Kim and L. A. Igneri
analysis showing no difference in survival, ROSC, hospital admission, 24-hour
survival, survival to hospital discharge, or neurologic outcome. The rate of intracranial hemorrhage was signicantly higher in patients who received tenecteplase
versus placebo (RR 6.95; 95% CI, 1.59–30.41; p = 0.006), highlighting safety
concerns with the administration of thrombolytics to all-comers with cardiac
arrest [11].
However, benet from thrombolytics may be seen in patients with conrmed
PE.A retrospective, observational, multicenter study of 14,253 adult patients with
OHCA reported outcomes among a total of 246 patients with conrmed PE.Fiftyeight patients were given thrombolytics as part of the resuscitative effort, with the
majority receiving tenecteplase (74%) followed by alteplase (24%). Thirty-day survival was higher in the thrombolysis group (16%) versus control (6%), p=0.005,
but no signicant difference in good neurologic recovery was seen (adjusted RR
1.97; 95% CI, 0.70–5.56) [43]. A recent systematic review and meta-analysis of
thrombolytic therapy in cardiac arrest from presumed or conrmed PE included 803
patients from 13 studies and found that IV thrombolysis was associated with higher
rates of ROSC (OR 2.55, 95% CI, 1.50–4.34), but no signicant difference in survival to hospital discharge (OR 1.41, 95% CI, 0.79–2.41) or bleeding complications
(OR 2.21, 95% CI, 0.95–5.17) [29]. Notably, there was signicant heterogeneity
among thrombolytic agent choice and dosing.
Based on these ndings, it is reasonable to attempt thrombolysis in conjunction
with standard resuscitative measures for cardiac arrest if there is conrmation of or
high suspicion of PE.
8.4.1.4 Contraindications toThrombolytic Therapy
Most contraindications to thrombolytic therapy that are traditionally utilized in
acute ischemic stroke should be considered relative in the setting of life-threatening,
high-risk PE as early thrombolytic intervention has been shown to improve inhospital mortality for hemodynamically unstable patients or those requiring
mechanical v
entilation [59, 97]. The pharmacist clinician should be familiar with
the contraindication and relative contraindication stratication based on PE severity, which are described in Table8.12.
8.4.2 Timing ofAnticoagulation inRelation toThrombolysis
In high-risk PE, it is important to initiate anticoagulation immediately while creating a plan for either systemic thrombolysis or alternative reperfusion therapies.
Historically, there has been discordance among major guidelines as to whether
heparin should be held during thrombolytic infusion administration. The 2008
CHEST guidelines suggest that it is acceptable to either continue or suspend UFH
infusion during thrombolytic administration as these two practices have never been
Acute Pulmonary Embolism
8
Table 8.12 Contraindications to thrombolytic therapy
Contraindications Relative Contraindications
High-risk PE Active internal bleeding.
Recent intracranial hemorrhage.
Intermediate-risk PEStructural intracranial disease.
Previous intracranial hemorrhage.
Ischemic stroke within 3months.
Active internal bleeding.
Recent brain or spinal surgery.
Recent head trauma with fracture or
brain injury.
Bleeding diathesis.
DBP diastolic blood pressure, PE pulmonary embolism, SBP systolic blood pressure
Reprinted from Ref. [39]
Structural intracranial disease.
Previous intracranial hemorrhage.
Ischemic stroke within 3months.
Recent brain or spinal surgery.
Recent head trauma with fracture or
brain injury.
Bleeding diathesis.
Pregnancy.
SBP >180mm Hg.
DBP >110mm Hg.
Recent bleeding (non-intracranial).
Recent surgery.
Recent invasive procedure.
Ischemic stroke >3months ago.
Anticoagulated.
Traumatic cardiopulmonary
resuscitation.
Pericarditis, pericardial uid.
Diabetic retinopathy.
Pregnancy.
Age >75years or low body weight
<65kg.
Female.
Black race.
199
compared. They cite that US regulatory bodies recommend suspension of IV UFH
during the 2-h alteplase 100mg infusion, but other countries may continue with IV
UFH while alteplase is infusing [47]. The 2014 ESC guidelines recommend that IV
UFH should be stopped during administration of streptokinase or urokinase, but
may be continued during alteplase infusion [57]. In cases when systemic thrombolysis is being administered, it is reasonable to continue IV UFH up until the initiation of alteplase infusion and discontinue while alteplase is infusing to reduce the
risk of bleeding events. After the 2-h alteplase infusion is complete, an activated
partial thromboplastin time (aPTT) should be assessed immediately, and UFH
should only be resumed once the aPTT is less than two times the patient’s baseline
(or 80seconds or less) [48]. A small study in healthy volunteers showed that aPTT
may be prolonged following alteplase administration [103]. Clinical judgment
should be used when determining the optimal time to restart IV UFH infusion,
especially for patients who had short durations or no exposure to IV UFH prior to
thrombolytic infusion. There is a paucity of evidence to guide an appropriate strategy for restarting heparin infusion based on anti-Xa monitoring, but it would be
reasonable to wait for the anti-Xa level to drop to 0.7units/mL or less before resuming heparin.
200
S. K. Kim and L. A. Igneri
8.5 Alternative Reperfusion Therapies (Surgical
Embolectomy, Endovascular Therapies)
8.5.1 Indications forInterventional Therapies
There are numerous interventional therapies performed for the management of PE,
including catheter-directed clot fragmentation or aspiration, mechanical embolectomy, local thrombolysis, and a combination of pharmaco-mechanical approaches
[86]. These techniques allow the restoration of pulmonary blood ow by relieving
the obstruction which improves RV function. Even partial recanalization of the pulmonary arteries can improve hemodynamic stability, and complete removal of the
thrombus is not always necessary.
There is a lack of high-quality controlled clinical trials that compare the efcacy
and safety of these various techniques. Therefore, catheter-directed therapies are not
currently considered rst-line. According to the 2019 ESC guidelines, CDT can be
considered for two categories of PE: high risk and intermediate-high risk. CDT can be
considered for patients with high-risk PE if they have contraindications to or failure of
systemic thrombolysis. Additionally, patients with intermediate-high-risk PE that
experience treatment failure with anticoagulation or have contraindications to or failure of systemic thrombolysis should also be considered for CDT [59]. The 2021
CHEST guideline recommends the consideration of interventional therapies for highrisk PE patients with shock, high risk of bleeding, or failure of systemic thrombolysis [99].
Treatment failure in the setting of PE management is not clearly dened or
agreed upon but generally describes a lack of improvement or further hemodynamic deterioration. Lack of hemodynamic improvement is assessed 2–4hours
after the completion of systemic thrombolysis, immediately after the completion
of local thrombolytic infusion, or 24–48hours after therapeutic anticoagulation.
Patients with a lack of improvement or progressively worsening hemodynamics
should be considered for rescue reperfusion therapy in discussion with members
of the PE response team (PERT). Patients who develop life-threatening cardiorespiratory instability (requiring CPR, mechanical ventilation, catecholamine
administration, or ECMO) should be evaluated emergently for treatment escalation [86].
8.5.2 Percutaneous Mechanical Interventions
Numerous techniques have been used for mechanical disruption or aspiration of
thrombus to treat PE without the use of pharmacologic thrombolysis (Table8.13).
Despite the lack of comparative efcacy data, these devices offer an alternative
treatment option for patients with contraindications to thrombolytic therapy [25].
Wire disruption, balloon fragmentation, and rotating pigtail catheters have been