Clinical trial NCT04149314: The "Hypotension Prediction Index" in Patients Undergoing Lung Surgery
Official title: PGDT With the "Hypotension Prediction Index" to Reduce the Number and Duration of Intraoperative Hypotension and the Incidence of Renal Failure in Patients Undergoing Lung Surgery
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Hypotension
Hemodynamic Instability
Renal Failure
Myocardial Injury
Anesthesia
Keywords: HPI
Thoracic Surgery
Single-Lung ventilation
Lead sponsor: University of Giessen
Sponsor class: OTHER
Collaborators: name: Edwards Lifesciences
First posted: 2019-11-04
Enrollment: 142
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The study is designed as a single center randomized prospective blinded interventional trial comparing goal directed hemodynamic management using HPI compared to standard care.
Primary purpose: TREATMENT

Brief summary: The "Hypotension Prediction Index (HPI)" was established by the Edwards Lifescience Company (Irvine, California, USA) and is CE certified. As part of the Edwards Acumen Decision-Support-Software-Suite the HPI is supported by the minimal invasive FloTrac Sensor. The HPI displays the probability of an occurring hypotension. The software was established with the help of 20.000 analyzed patient events. If the upper limit of the HPI is reached, the software is alarming the treating physician 8. At the university hospital of Giessen HPI analyses are used in the daily clinical routine as well as for scientific purposes. Preliminary data of the HPI-I-Trial ("Influence of the Hypotension Prediction Index on the number and duration of intraoperative hypotension in primary hip-endoprothetic replacement", University Hospital of Giessen) included patients, which underwent hip-endoprothetic replacement surgery and revealed that the use of HPI with a goal directed therapy (GDT) protocol compared to standard care significantly reduced the incidence and duration of intraoperative hypotension. Therefore HPI with GDT might reduce the incidence of hypotension related complications in a sicker patient cohort.

The aim of the study is to investigate whether a goal directed treatment according to the Hypotension Prediction Index compared to standard care can reduce the incidence of intraoperative hypotension in patients under single lung ventilation.

Detailed description: Monitoring of blood pressure is a basic tool to assess the patients' hemodynamic status. Physiological blood pressure is usually close to 120/80 mmHg. Hypotension is not clearly defined as shown in previous studies 1, 20, 21. Some studies defined hypotension as a systolic blood pressure below 100 mmHg or a mean arterial pressure below 60 mmHg 1,2. Depending on the definition intraoperative hypotension (IOH) hypotension can occur in 38% of patients undergoing non-cardiac surgery. 53% of these patients die within one year. Monk et al. noted that the 1-year-mortality was raised by 3.6% for every minute the systolic blood pressure was below 80 mmHg. The risk of mortality was raised up to 1.4 times when the MAP was under 55 mmHg for more than 10 minutes 3. Additionally, in 2015 it was shown that even short duration of MAP under 55 mmHg is associated with a high risk for acute kidney injury and myocardial infarction 4. A recent definition of hypotension was published by of Vernooij et al. that defined IOH as a decrease of MAP \< 65 mmHg for more than one minute in this study 22. Perioperative hypotension is a complication that can occur in the induction period and in the following phase. Recent unpublished data from the Sessler group presented at the 2018 ASA meeting in San Francisco showed that about 1/3 of hypotensive episodes are unrelated to surgery as those occur before the surgeon is in the OR 28. The reasons for hypotension can be found in vasodilatation (e. g. drug induced), volume deficit (based on blood loss), or negative inotropic effect of surgery and anesthetic drugs (reduced left ventricular function). Main factors causing intraoperative hypotension according to literature are age, preexisting diseases (especially ASA \> 3), duration of surgery, acuteness of surgery (emergency), anti-hypertensive medication and anesthesia combining general and regional anesthesia 5,6. Complications related to hypotension can be detected in most organ systems. One important source of hypotension-associated complications are cardiovascular complications. Recently, a syndrome that was termed myocardial injury after non-cardiac surgery (MINS) was shown to be associated with hypotension and lead to increased postoperative mortality rate 23, 24. Acute kidney injury (AKI) affects up to 25% of patients in the intensive care unit 7. Liu et al. described that an episode of relative hypotension is often followed by AKI (a decrease in systolic blood pressure relative to pre-morbid value was a significant independent predictor of the development of AKI and of RIFLE classes I and F; odds ratio 1.084 for every -1 mmHg change in systolic blood pressure) 8. As stated, 'normotensive renal failure' is not common and a rare phenomenon in the absence of septic and other complications. This results are supported by other publications, like Lehmann et al. 9. Their results indicate that the risk of AKI was related to the severity of hypotension with an odds ratio (OR) of 1.03, 95% CI 1.02-1.04 (p \< 0.0001) per 1 mmHg decrease in minimum MAP ≥ 80 mmHg. For each additional hour MAP was less than 70, 60, 50 mmHg, the risk of AKI increased by 2% (OR 1.02, 95% CI 1.00-1.03, p = 0.0034), 5% (OR 1.05, 95% CI 1.02-1.08, p = 0.0028), and 22% (OR 1.22, 95% CI 1.04-1.43, p = 0.0122).

Renal failure poses a relevant complication in the perioperative phase 5, 6. Over the last decade the cell cycle arrest biomarkers TIMP-2- and IGFBP7-quantification (Nephrocheck) has been successfully evaluated for the detection of AKI 7. The main advantage of both parameters is the opportunity of early detection of AKI and its point-of-care design, which makes them especially for the use on the intensive care unit valuable. Based on these facts, the predictive measurement of blood pressure is of great interest for the anesthesiologist to optimize patients' postoperative outcome.

The "Hypotension Prediction Index (HPI)" was established by the Edwards Lifescience Company (Irvine, California, USA) and is CE certified. As part of the Edwards Acumen Decision-Support-Software-Suite the HPI is supported by the minimal invasive FloTrac Sensor. The HPI displays the probability of an occurring hypotension. The software was established with the help of 20.000 analyzed patient events. If the upper limit of the HPI is reached, the software is alarming the treating physician 8. At the university hospital of Giessen HPI analyses are used in the daily clinical routine as well as for scientific purposes. Preliminary data of the HPI-I-Trial ("Influence of the Hypotension Prediction Index on the number and duration of intraoperative hypotension in primary hip-endoprothetic replacement", University Hospital of Giessen) included patients, which underwent hip-endoprothetic replacement surgery and revealed that the use of HPI with a goal directed therapy (GDT) protocol compared to standard care significantly reduced the incidence and duration of intraoperative hypotension. Therefore HPI with GDT might reduce the incidence of hypotension related complications in a sicker patient cohort.

The development of modern lung surgery started in the 19th century. Especially in Germany Rudolf Nissen (first pneumonectomy, 1931) and Ferdinand Sauerbruch were the first pioneers of lung surgery. With enhancement and refinement of thoracic anesthesiology (lung separation) and further specialization of surgery, thoracic surgery became a seperate discipline. During thoracic surgery lung separation and isolation with accomplished single-lung ventilation plays a key role in the development of thoracic surgery. Spectrum of indication contains thoracic surgery, procedure- and patient-dependent factors. Usually lung isolation is achieved with a double-lumen tube or a bronchial blocker. Major domain of thoracic surgery is nowadays oncological surgery of lung cancer. With modern imaging lung cancer is detected in early stage, so more operations can be performed. Additional in the last thirty years more and more minimal invasive procedures (VATS) were performed which result in gentle and successful treatment of thoracic surgical patients.

Beside oncological surgeries (which make almost 50% of all procedures in thoracic surgery) plays surgery of inflammable diseases and pulmonary emphysema a major role.

Approximately 182.821 thoracic surgical procedures are performed in Germany, 11.451 in Hessen. At the university clinic institution of Giessen more than 500 procedures are performed per year.

Hypotension Prediction Index The "Hypotension Prediction Index (HPI) "was established by the Edwards Lifescience Company (Irvine, USA) and is CE certified. The HPI displays the probability of an occurring hypotension before its onset and therefore can theoretically prevent episodes of hypotension by guiding earlier therapy. This might improve outcome in certain patient populations by preventing episodes of hypotension 29. A recent paper describes the methodology of this prediction tool 25.

Nephro Check NephroCheck is a point of care urine test that flags two biomarkers that indicate if a critically ill patient is at risk for acute kidney injury (AKI) 15. Currently, serum creatinine is the main test used to detect AKI, but it may take a day or more for serum creatinine levels to accumulate in the blood of a patient with a kidney injury consequently, it may not reflect real time kidney damage or loss of function 16. Results of the NephroCheck test are available within 20 minutes before clinical signs of kidney failure are apparent. The evidence suggests that the NephroCheck test has good sensitivity (89% at the 0.3 cutoff value) for detecting critically ill patients at risk for AKI 17, 18.

The aim of the study is to investigate whether a goal directed treatment according to the Hypotension Prediction Index compared to standard care can reduce the incidence of intraoperative hypotension in patients under single lung ventilation.

Eligibility criteria: Inclusion Criteria:

* Patients undergoing lung surgery with one-lung-ventilation
* General anesthesia
* Age ≥ 18 years

Exclusion Criteria:

* Participation in another (interventional) study
* Pregnancy and nursing mothers
* Surgery without controlled ventilation
* ASA I or IV
* Contraindication for invasive blood pressure monitoring
* Coagulation disorder
* Arterial Fibrillation

Primary outcomes:
measure: Incidence of intraoperative hypotension
timeFrame: up to 8 hours
Secondary outcomes:
measure: Renal failure
timeFrame: preoperative, immediately after operation and day 1 after operation
measure: Concentration of troponin
timeFrame: preoperative, immediately after operation and day 1 after operation
measure: Hemodynamic status
timeFrame: up to 8 hours
measure: Procedual Data
timeFrame: until the end of anesthesia
measure: POMS (Postoperative Morbidity Survey Score)
timeFrame: day 1, 3 and 5 after operation
measure: Circulation supportive mediaction
timeFrame: from beginning until the end of surgery
measure: Hospital stay
timeFrame: From admission to hospital until discharge of hospital up to 18 month
measure: Mortality after surgery
timeFrame: up to 180 days after surgery
Other outcomes:
Locations:
city: Gießen
country: Germany
facility: Univeristy of Giessen
state: Hessen
Study officials:
affiliation: Study Chair, Head of Department
name: Michael Sander, Prof.
role: STUDY_CHAIR
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