Perioperative use of crystalloids in patients undergoing open radical cystectomy: balanced Ringer’s maleate vs G5-K solution

ISRCTN ISRCTN32976792
DOI https://doi.org/10.1186/ISRCTN32976792
Secondary identifying numbers 151/13
Submission date
30/10/2013
Registration date
21/11/2013
Last edited
14/08/2020
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Urological and Genital Diseases
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data

Plain English summary of protocol

Background and study aims
Infections of the bladder (cystitis) can affect the bladder, kidney and the connecting tubes. Sometimes this require a cystectomy, which a surgery to remove all or part of the bladder, requiring urinary diversion (the urine is flow is changed). When patients undergo a cystectomy, they are prone to having issues with their salt and water balance. They often require hydration during the surgery and while in hospital, but the choice of what the optimal crystalloid solution (ie. The balance of water and salt) is still unclear. In addition, it has been demonstrated that the influence of salt and water balance on gastrointestinal recovery after colonic surgery is clinically relevant: patients receiving less fluid and less sodium show faster recovery of gastrointestinal function, resulting in a shorter hospitalization time. This is of crucial importance in cystectomy patients because they are at risk for postoperative constipation (not able to pass stool regularly) or ileus (buildup or blockages in the bowels). The aim of this study is so evaluate the physiology of electrolyte and water homeostasis in patients undergoing open cystectomy with urinary diversion using two different fluid regimes.

Who can participate?
Adults aged 18 and older who have cystectomy with urinary diversion

What does the study involve?
Participants are randomly allocated to one of two groups. Those in the first group receive the Ringerfundin solution. Those in the second group receive the G5-K crystalloid solution at baseline, and during the operation. After the surgery, they receive the same type of hydration. Blood samples are taken prior to the surgery and at six hours after the surgery, as well as days one, two, three and four after the surgery.

What are the possible benefits and risks of participating?
Not provided at time of registration.

Where is the study run from?
University Hospital of Bern (Switzerland)

When is the study starting and how long is it expected to run for?
December 2013 to June 2015

Who is funding the study?
University Hospital of Bern (Switzerland)

Who is the main contact?
Dr Patrick Wuethrich
patrick.wuethrich@insel.ch

Contact information

Dr Patrick Wuethrich
Scientific

Department of Anaesthesiology and Pain Therapy
University Hospital Bern Inselspital Bern
Berne
3010
Switzerland

Phone +41 (0)31 632 27 25
Email patrick.wuethrich@insel.ch

Study information

Study designRandomized parallel-group single-centre interventional assessor blind trial
Primary study designInterventional
Secondary study designRandomised controlled trial
Study setting(s)Hospital
Study typeTreatment
Participant information sheet Not available in web format, please use the contact details below to request a patient information sheet
Scientific titlePerioperative use of crystalloids in patients undergoing open radical cystectomy: balanced Ringer’s maleate vs G5-K solution - a randomized clinical trial
Study objectivesWe hypothesize that an approach with glucose-potassium-based and less chloride crystalloid solution will result in a faster return of bowel function, less hypernatriemia and hyperchloremic metabolic acidosis with less frequent hyper-osmolality and a better maintained fluid balance compared to a regimen with a balanced Ringer's crystalloid solution.

On 09/06/2015 the overall trial date was changed from 31/12/2016 to 09/06/2015.
Ethics approval(s)Ethics Committee of the Canton of Bern (Kantonale Ethikkommission), Berne, Switzerland, 22/10/2013, ref: 151/13
Health condition(s) or problem(s) studiedBladder disease resulting in cystectomy and urinary diversion
InterventionAccording to the randomization, an equal number of patients will be allocated to receive the Ringerfundin® solution or the G5-K crystalloid solution as baseline infusion during the whole time that an intravenous administration of fluid is necessary. The G5-K solution is already used as a baseline infusion on our intensive care unit and has been shown to be safe.

Intraoperatively: After induction of anesthesia, a concomitant norepinephrine infusion will be started at 2 µg·kg-1·h-1 until the end of surgery and the randomized crystalloid solution (Ringerfundin®, B.Braun Medical AG, Sempach), Switzerland for group 1 or the G5-K solution for group 2 (Bichsel, Interlaken, Switzerland) will be infused at a rate of 1 ml·kg-1·h-1 until the bladder has been removed, followed by 3 ml·kg-1·h-1 until the end of surgery. If hypotension is observed (mean arterial pressure (MAP) <60 mmHg), norepinephrine will be titrated to maximum 8 µg·kg-1·h-1 after an initial bolus of 10 µg. If hypotension persists; a bolus of 250 ml of randomized crystalloid solution will be given.
In both groups, a blood loss >500 ml will be substituted with an equal amount of balanced Ringer’s solution (Ringerfundin®). Packed red blood cells (PRBC) will be transfused if hemoglobin values are <80 g/l (<100 g/l in patients with coronary artery disease). Additional boluses of Ringerfundin® (250 ml) will be infused as a rescue medication if a MAP <60 mmHg persists after the above mentioned correction, and in case of severe intraoperative metabolic acidosis (base excess <-5, pH <7.25) attributable to severe hypovolemia.
Postoperatively: Postoperative hydration will be identical in both groups and will consist primarily of 1500 ml of the randomized crystalloid solution per 24 hours. If the MAP is <60 mmHg after a bolus of 500 ml of balanced Ringer’s solution, norepinephrine will be infused up to a rate of 200 µg/h in both groups. PRBC units will be transfused according to the ASA guidelines and fresh frozen plasma units will be given if the prothrombin time is >1.5 times normal values.
In both groups, patients will be allowed to drink clear fluids immediately after surgery on the intermediate care unit. A peroral liquid diet will be started on POD 1 as well as active mobilization. To enhance recovery of bowel function, the use of chewing gum will be encouraged and the subcutaneous application of neostigmine 0.5 mg will be started on POD 2. Body weight will be measured daily in the morning. Time of first flatus and first defecation will be recorded.

Time course of the study:
Admission day: After informed consent, patients undergoing open radical cystectomy with urinary diversion will be randomized, according to the concealed numbered envelopes. Preoperative blood samples will be taken (plasma samples: Na, K, Cl, Mg, HPO4, Glc, osmolality, renin, aldosterone, arginin-vasopressin, BNP; urine NGAL, Na, Cl and osmolality) and body weight documented. Patients included will be informed to note the time of the first flatus and to inform the nurses accordingly.
6 h postoperative: Blood samples will be taken (arterial blood gas analysis, plasma samples: Na, K, Cl, Mg, HPO4, Glc, osmolality, renin, aldosterone, arginine-vasopressin, BNP; urine: NGAL, Na, Cl and osmolality).
Postoperative day 1: Blood samples will be taken (arterial blood gas analysis, plasma samples: Na, K, Cl, Mg, HPO4, Glc, osmolality, renin, aldosterone, arginine-vasopressin, BNP; urine: NGAL, Na, Cl and osmolality). Body weight and assessment of flatus and defecation will be documented.
Postoperative day 2: Blood samples will be taken (arterial blood gas analysis, plasma samples: Na, K, Cl, Mg, HPO4, Glc, osmolality, renin, aldosterone, arginine-vasopressin, BNP; urine: NGAL, Na, Cl and osmolality). Body weight and assessment of flatus and defecation will be documented.
Postoperative day 3: Blood samples will be taken (arterial blood gas analysis, plasma samples: Na, K, Cl, Mg, HPO4, Glc, osmolality, renin, aldosterone, arginine vasopressin, BNP; urine samples: NGAL, Na, Cl and osmolality). Body weight and assessment of flatus and defecation will be documented.
Postoperative day 4: Blood samples will be taken (arterial blood gas analysis, plasma samples: Na, K, Cl, Mg, HPO4, Glc, osmolality, renin, aldosterone, arginine vasopressin, BNP; urine samples: NGAL, Na, Cl and osmolality). Body weight and assessment of flatus and defecation will be documented.

Added 11/09/2014: the trial is now recruiting participants.
Intervention typeDrug
Pharmaceutical study type(s)
PhaseNot Applicable
Drug / device / biological / vaccine name(s)Ringerfundin, G5-K crystalloid solution
Primary outcome measureFirst defecation (return of bowel function) postoperatively
Secondary outcome measures1. First flatus
2. Positive fluid balance (body weight difference postoperatively vs preoperatively)
3. Incidence of kidney function disorders according to the RIFLE classification
4. Difference in pH 24 h postoperatively (metabolic acidosis defined as hyperchloremia, normal anion gap, low plasma bicarbonate)
5. Changes in plasma and urine osmolality during the duration of infusion
6. Incidence of hypernatriemia during the duration of infusion
7. Incidence of hyperchloremia during the duration of infusion
8. Incidence of hypokaliemia during the duration of infusion
9. Changes in plasma renin, aldosterone, arginin vasopressin and brain natriuretic peptide (BNP) levels
10. Changes in neutrophil gelatinase-associated lipocalin (NGAL) urine values
Overall study start date01/12/2013
Completion date09/06/2015

Eligibility

Participant type(s)Patient
Age groupAdult
Lower age limit18 Years
SexBoth
Target number of participants44
Total final enrolment44
Key inclusion criteria1. Aged 18 years or over
2. Cystectomy with urinary diversion
3. American Society of Anaesthesiologists (ASA) classification II and III
4. Informed consent
Key exclusion criteria1. Pregnant, breastfeeding women (exclusion for surgery per se)
2. Congestive heart failure [New York Heart Association (NYHA) classification ≥3]
3. Hepatic disease (prothrombin ratio <50%)
4. Significant renal dysfunction (estimated glomerular filtration rate <45 ml/min)
Date of first enrolment14/07/2014
Date of final enrolment26/05/2015

Locations

Countries of recruitment

  • Switzerland

Study participating centre

University Hospital Bern Inselspital Bern
Berne
3010
Switzerland

Sponsor information

Bern University Hospital (Switzerland)
Hospital/treatment centre

c/o Patrick Wuethrich, M.D.
Department of Anaesthesiology and Pain Therapy
Inselspital Bern
Berne
3010
Switzerland

Phone +41 (0)31 632 27 25
Email patrick.wuethrich@insel.ch
ROR logo "ROR" https://ror.org/01q9sj412

Funders

Funder type

Hospital/treatment centre

Bern University Hospital (Switzerland) - Department of Urology and Anesthesiology / Pain Treatment

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryNot provided at time of registration
Publication and dissemination planNot provided at time of registration
IPD sharing plan

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
Protocol article protocol 08/07/2014 Yes No
Results article results 01/10/2016 14/08/2020 Yes No

Editorial Notes

14/08/2020: Publication reference and total final enrolment number added.
25/052017: Plain English summary added.