Trial Outcomes & Findings for Effect of Goal-directed Crystalloid Versus Colloid Administration on Major Postoperative Morbidity (NCT NCT01195883)

NCT ID: NCT01195883

Last Updated: 2018-10-30

Results Overview

Any of the following major complications: (1) Cardiac (Acute heart failure/Myocardial infarction/Ventricular arrhythmia); (2) pulmonary (embolism/edema/respiratory failure/pneumonia/pleural effusion); (3) gastrointestinal (bowel and surgical anastomosis stricture or anastomotic leak/internal or external fistulas/peritoneal effusions); (4) Renal (requiring dialysis); (5) Infectious (deep or organ space surgical site infection / sepsis); and (6) Coagulation (bleeding).

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 1102 participants
• Primary outcome timeframe: Postoperative 30-days
• Results posted on: 2018-10-30

Participant Flow

Participant milestones

Measure	Crystalloid Lactated Ringers solution will be used for fluid replacement. Crystalloid: For goal directed volume management we use corrected aortic flow time (FTc) and stroke volume derived from esophageal Doppler as in previous studies. In case of hypovolemia, detected by esophageal Doppler monitoring (CardioQ, Deltex Medical Group PLC, Chichester, UK) according to a previously published algorithm, an additional fluid bolus of 250 ml of LR will be given over a period of 5 minutes.	Colloid Low-molecular weight colloid HES 130/0.4 (Voluven) will be used for fluid replacement Colloid: For goal directed volume management we use corrected aortic flow time (FTc) and stroke volume derived from esophageal Doppler as in previous studies. In case of hypovolemia, detected by esophageal Doppler monitoring (CardioQ, Deltex Medical Group PLC, Chichester, UK) according to a previously published algorithm, an additional fluid bolus of 250 ml of Hydroxyethylstarch 6% 130/0.4 (Voluven®Fresenius-Kabi, Bad Homburg, Germany) will be given over a period of 5 minutes.
Overall Study STARTED	553	549
Overall Study COMPLETED	534	523
Overall Study NOT COMPLETED	19	26

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Effect of Goal-directed Crystalloid Versus Colloid Administration on Major Postoperative Morbidity

Baseline characteristics by cohort

Measure	Crystalloid n=534 Participants Lactated Ringers solution will be used for fluid replacement. Crystalloid: For goal directed volume management we use corrected aortic flow time (FTc) and stroke volume derived from esophageal Doppler as in previous studies. In case of hypovolemia, detected by esophageal Doppler monitoring (CardioQ, Deltex Medical Group PLC, Chichester, UK) according to a previously published algorithm, an additional fluid bolus of 250 ml of LR will be given over a period of 5 minutes.	Colloid n=523 Participants Low-molecular weight colloid HES 130/0.4 (Voluven) will be used for fluid replacement Colloid: For goal directed volume management we use corrected aortic flow time (FTc) and stroke volume derived from esophageal Doppler as in previous studies. In case of hypovolemia, detected by esophageal Doppler monitoring (CardioQ, Deltex Medical Group PLC, Chichester, UK) according to a previously published algorithm, an additional fluid bolus of 250 ml of Hydroxyethylstarch 6% 130/0.4 (Voluven®Fresenius-Kabi, Bad Homburg, Germany) will be given over a period of 5 minutes.	Total n=1057 Participants Total of all reporting groups
Age, Continuous	52 years STANDARD_DEVIATION 16 • n=5 Participants	52 years STANDARD_DEVIATION 16 • n=7 Participants	52 years STANDARD_DEVIATION 16 • n=5 Participants
Sex: Female, Male Female	268 Participants n=5 Participants	242 Participants n=7 Participants	510 Participants n=5 Participants
Sex: Female, Male Male	266 Participants n=5 Participants	281 Participants n=7 Participants	547 Participants n=5 Participants

PRIMARY outcome

Timeframe: Postoperative 30-days

Any of the following major complications: (1) Cardiac (Acute heart failure/Myocardial infarction/Ventricular arrhythmia); (2) pulmonary (embolism/edema/respiratory failure/pneumonia/pleural effusion); (3) gastrointestinal (bowel and surgical anastomosis stricture or anastomotic leak/internal or external fistulas/peritoneal effusions); (4) Renal (requiring dialysis); (5) Infectious (deep or organ space surgical site infection / sepsis); and (6) Coagulation (bleeding).

Outcome measures

Measure	Crystalloid n=534 Participants Lactated Ringers solution will be used for fluid replacement. Crystalloid: For goal directed volume management we use corrected aortic flow time (FTc) and stroke volume derived from esophageal Doppler as in previous studies. In case of hypovolemia, detected by esophageal Doppler monitoring (CardioQ, Deltex Medical Group PLC, Chichester, UK) according to a previously published algorithm, an additional fluid bolus of 250 ml of LR will be given over a period of 5 minutes.	Colloid n=523 Participants Low-molecular weight colloid HES 130/0.4 (Voluven) will be used for fluid replacement Colloid: For goal directed volume management we use corrected aortic flow time (FTc) and stroke volume derived from esophageal Doppler as in previous studies. In case of hypovolemia, detected by esophageal Doppler monitoring (CardioQ, Deltex Medical Group PLC, Chichester, UK) according to a previously published algorithm, an additional fluid bolus of 250 ml of Hydroxyethylstarch 6% 130/0.4 (Voluven®Fresenius-Kabi, Bad Homburg, Germany) will be given over a period of 5 minutes.
Number of Participants With Postoperative Morbidity (Major Complications)	103 Participants	91 Participants

SECONDARY outcome

Timeframe: Postoperative 30-days

Any of the following minor complications: (1) unplanned ICU admission; (2) unplanned operation; (3) cardiac (ischemia/non-ventricular arrhythmia/hemodynamic disturbances); (4) pulmonary effusion; (5) deep venous thrombosis; (6) gastrointestinal (effusion/gut paralysis); (7) progressive renal insufficiency; (8) infection (superficial/fever/cystitis or urinary tract infection); and (9) transient neurological injury.

Outcome measures

Measure	Crystalloid n=463 Participants Lactated Ringers solution will be used for fluid replacement. Crystalloid: For goal directed volume management we use corrected aortic flow time (FTc) and stroke volume derived from esophageal Doppler as in previous studies. In case of hypovolemia, detected by esophageal Doppler monitoring (CardioQ, Deltex Medical Group PLC, Chichester, UK) according to a previously published algorithm, an additional fluid bolus of 250 ml of LR will be given over a period of 5 minutes.	Colloid n=447 Participants Low-molecular weight colloid HES 130/0.4 (Voluven) will be used for fluid replacement Colloid: For goal directed volume management we use corrected aortic flow time (FTc) and stroke volume derived from esophageal Doppler as in previous studies. In case of hypovolemia, detected by esophageal Doppler monitoring (CardioQ, Deltex Medical Group PLC, Chichester, UK) according to a previously published algorithm, an additional fluid bolus of 250 ml of Hydroxyethylstarch 6% 130/0.4 (Voluven®Fresenius-Kabi, Bad Homburg, Germany) will be given over a period of 5 minutes.
Number of Participants With Postoperative Morbidity (Minor Complications)	234 Participants	214 Participants

SECONDARY outcome

Timeframe: Postoperative 30 days

A composite of the primary outcome, and readmission and death.

Outcome measures

Measure	Crystalloid n=525 Participants Lactated Ringers solution will be used for fluid replacement. Crystalloid: For goal directed volume management we use corrected aortic flow time (FTc) and stroke volume derived from esophageal Doppler as in previous studies. In case of hypovolemia, detected by esophageal Doppler monitoring (CardioQ, Deltex Medical Group PLC, Chichester, UK) according to a previously published algorithm, an additional fluid bolus of 250 ml of LR will be given over a period of 5 minutes.	Colloid n=518 Participants Low-molecular weight colloid HES 130/0.4 (Voluven) will be used for fluid replacement Colloid: For goal directed volume management we use corrected aortic flow time (FTc) and stroke volume derived from esophageal Doppler as in previous studies. In case of hypovolemia, detected by esophageal Doppler monitoring (CardioQ, Deltex Medical Group PLC, Chichester, UK) according to a previously published algorithm, an additional fluid bolus of 250 ml of Hydroxyethylstarch 6% 130/0.4 (Voluven®Fresenius-Kabi, Bad Homburg, Germany) will be given over a period of 5 minutes.
Number of Participants With Postoperative Complications, 30-day Readmission, and 30-day Death	143 Participants	125 Participants

SECONDARY outcome

Timeframe: Hospitalization

Preoperative-to-postoperative change in AKIN stage

Outcome measures

Measure	Crystalloid n=527 Participants Lactated Ringers solution will be used for fluid replacement. Crystalloid: For goal directed volume management we use corrected aortic flow time (FTc) and stroke volume derived from esophageal Doppler as in previous studies. In case of hypovolemia, detected by esophageal Doppler monitoring (CardioQ, Deltex Medical Group PLC, Chichester, UK) according to a previously published algorithm, an additional fluid bolus of 250 ml of LR will be given over a period of 5 minutes.	Colloid n=521 Participants Low-molecular weight colloid HES 130/0.4 (Voluven) will be used for fluid replacement Colloid: For goal directed volume management we use corrected aortic flow time (FTc) and stroke volume derived from esophageal Doppler as in previous studies. In case of hypovolemia, detected by esophageal Doppler monitoring (CardioQ, Deltex Medical Group PLC, Chichester, UK) according to a previously published algorithm, an additional fluid bolus of 250 ml of Hydroxyethylstarch 6% 130/0.4 (Voluven®Fresenius-Kabi, Bad Homburg, Germany) will be given over a period of 5 minutes.
Number of Participants With Postoperative Acute Kidney Injury	21 Participants	16 Participants

Adverse Events

Crystalloid

Serious events: 103 serious events

Other events: 234 other events

Deaths: 4 deaths

Colloid

Serious events: 91 serious events

Other events: 214 other events

Deaths: 5 deaths

Serious adverse events

Measure	Crystalloid n=534 participants at risk Lactated Ringers solution will be used for fluid replacement. Crystalloid: For goal directed volume management we use corrected aortic flow time (FTc) and stroke volume derived from esophageal Doppler as in previous studies. In case of hypovolemia, detected by esophageal Doppler monitoring (CardioQ, Deltex Medical Group PLC, Chichester, UK) according to a previously published algorithm, an additional fluid bolus of 250 ml of LR will be given over a period of 5 minutes.	Colloid n=523 participants at risk Low-molecular weight colloid HES 130/0.4 (Voluven) will be used for fluid replacement Colloid: For goal directed volume management we use corrected aortic flow time (FTc) and stroke volume derived from esophageal Doppler as in previous studies. In case of hypovolemia, detected by esophageal Doppler monitoring (CardioQ, Deltex Medical Group PLC, Chichester, UK) according to a previously published algorithm, an additional fluid bolus of 250 ml of Hydroxyethylstarch 6% 130/0.4 (Voluven®Fresenius-Kabi, Bad Homburg, Germany) will be given over a period of 5 minutes.
Cardiac disorders Cardiac	1.5% 8/534 • Number of events 8 • 30-days postoperative Adverse Events were monitored/assessed in such a manner that the specific Adverse Event Terms did not be recorded.	0.19% 1/523 • Number of events 1 • 30-days postoperative Adverse Events were monitored/assessed in such a manner that the specific Adverse Event Terms did not be recorded.
Respiratory, thoracic and mediastinal disorders Pulmonary	4.5% 24/534 • Number of events 24 • 30-days postoperative Adverse Events were monitored/assessed in such a manner that the specific Adverse Event Terms did not be recorded.	3.3% 17/523 • Number of events 17 • 30-days postoperative Adverse Events were monitored/assessed in such a manner that the specific Adverse Event Terms did not be recorded.
Gastrointestinal disorders Gastrointestinal	9.6% 51/534 • Number of events 51 • 30-days postoperative Adverse Events were monitored/assessed in such a manner that the specific Adverse Event Terms did not be recorded.	7.8% 41/523 • Number of events 41 • 30-days postoperative Adverse Events were monitored/assessed in such a manner that the specific Adverse Event Terms did not be recorded.
Renal and urinary disorders Renal	0.75% 4/534 • Number of events 4 • 30-days postoperative Adverse Events were monitored/assessed in such a manner that the specific Adverse Event Terms did not be recorded.	0.38% 2/523 • Number of events 2 • 30-days postoperative Adverse Events were monitored/assessed in such a manner that the specific Adverse Event Terms did not be recorded.
Infections and infestations infections	10.9% 58/534 • Number of events 58 • 30-days postoperative Adverse Events were monitored/assessed in such a manner that the specific Adverse Event Terms did not be recorded.	11.3% 59/523 • Number of events 59 • 30-days postoperative Adverse Events were monitored/assessed in such a manner that the specific Adverse Event Terms did not be recorded.
Vascular disorders Coagulation	2.2% 12/534 • Number of events 12 • 30-days postoperative Adverse Events were monitored/assessed in such a manner that the specific Adverse Event Terms did not be recorded.	3.1% 16/523 • Number of events 16 • 30-days postoperative Adverse Events were monitored/assessed in such a manner that the specific Adverse Event Terms did not be recorded.

Other adverse events

Measure	Crystalloid n=534 participants at risk Lactated Ringers solution will be used for fluid replacement. Crystalloid: For goal directed volume management we use corrected aortic flow time (FTc) and stroke volume derived from esophageal Doppler as in previous studies. In case of hypovolemia, detected by esophageal Doppler monitoring (CardioQ, Deltex Medical Group PLC, Chichester, UK) according to a previously published algorithm, an additional fluid bolus of 250 ml of LR will be given over a period of 5 minutes.	Colloid n=523 participants at risk Low-molecular weight colloid HES 130/0.4 (Voluven) will be used for fluid replacement Colloid: For goal directed volume management we use corrected aortic flow time (FTc) and stroke volume derived from esophageal Doppler as in previous studies. In case of hypovolemia, detected by esophageal Doppler monitoring (CardioQ, Deltex Medical Group PLC, Chichester, UK) according to a previously published algorithm, an additional fluid bolus of 250 ml of Hydroxyethylstarch 6% 130/0.4 (Voluven®Fresenius-Kabi, Bad Homburg, Germany) will be given over a period of 5 minutes.
Surgical and medical procedures Minor unplanned operation	4.3% 23/534 • Number of events 23 • 30-days postoperative Adverse Events were monitored/assessed in such a manner that the specific Adverse Event Terms did not be recorded.	5.5% 29/523 • Number of events 29 • 30-days postoperative Adverse Events were monitored/assessed in such a manner that the specific Adverse Event Terms did not be recorded.
Cardiac disorders Cardiac	8.6% 46/534 • Number of events 46 • 30-days postoperative Adverse Events were monitored/assessed in such a manner that the specific Adverse Event Terms did not be recorded.	6.7% 35/523 • Number of events 35 • 30-days postoperative Adverse Events were monitored/assessed in such a manner that the specific Adverse Event Terms did not be recorded.
Respiratory, thoracic and mediastinal disorders Pulmonary effusion	8.6% 46/534 • Number of events 46 • 30-days postoperative Adverse Events were monitored/assessed in such a manner that the specific Adverse Event Terms did not be recorded.	7.3% 38/523 • Number of events 38 • 30-days postoperative Adverse Events were monitored/assessed in such a manner that the specific Adverse Event Terms did not be recorded.
Gastrointestinal disorders Gastrointestinal	19.3% 103/534 • Number of events 103 • 30-days postoperative Adverse Events were monitored/assessed in such a manner that the specific Adverse Event Terms did not be recorded.	14.3% 75/523 • Number of events 75 • 30-days postoperative Adverse Events were monitored/assessed in such a manner that the specific Adverse Event Terms did not be recorded.
Infections and infestations Infection	28.3% 151/534 • Number of events 151 • 30-days postoperative Adverse Events were monitored/assessed in such a manner that the specific Adverse Event Terms did not be recorded.	26.6% 139/523 • Number of events 139 • 30-days postoperative Adverse Events were monitored/assessed in such a manner that the specific Adverse Event Terms did not be recorded.

Additional Information

Daniel I. Sessler, MD

Cleveland Clinic

Phone: 216-444-4900

Email: DS@OR.org

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place