Prostate CancerBLISSS2NCT01968447
Effect of Neuromuscular Block and Arterial PCO2 on Surgical Rating Scale (SRS), Following Reversal With Sugammadex
A study testing hypocapnia and normocapnia in people with Prostate Cancer and Renal Cancer, run by Leiden University Medical Center at 1 site in Netherlands.
Trial summary
The purpose of this study is to study the effect of variations in the arterial CO2 concentration during deep neuromuscular block on the surgical conditions as assessed by the surgical rating scale Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Prostate Cancer, Renal Cancer
- What is being tested?
- hypocapnia and normocapnia
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteNetherlands
- Study dates
- Feb 2014to Oct 2015
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- (i) Patients diagnosed with renal or prostatic disease who are will undergo an elective laparoscopic renal surgical procedure or laparoscopic prostatectomy;
- (ii) ASA class I-III
- (iii) > 18 years of age;
- (iv) Ability to give oral and written informed consent.
Who cannot join
- (i) Known or suspected neuromuscular disorders impairing neuromuscular function;
- (ii) Allergies to muscle relaxants, anesthetics or narcotics;
- (iii) A (family) history of malignant hyperthermia;
- (iv) Women who are or may be pregnant or are currently breast feeding;
- (v) Renal insufficiency, as defined by serum creatinine x 2 of normal, or urine output < 0.5 ml/kg/h for at least 6 h. When available, other indices will be taken into account as well such as glomerular filtration rate < 60 ml/h and proteinuria (a ratio of 30 mg albumin to 1 g of creatinine).
- (vi) Previous retroperitoneal surgery at the site of the current surgery.
Show all 9Show fewer
- (vii) Body mass index > 35 kg/m2
- (viii) Chronic obstructive pulmonary disease GOLD 2-4 or a FEV1 less than 70% predicted or VC less than 70% predicted
- (ix) chronic pulmonary disease with altered lung physiology (eg. sarcoidosis, cycstic fibrosis, obstructing pulmonary tumors, previous lung surgery)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Effect of Deep Neuromuscular Block and Variations in Arterial PCO2 on the Surgical Rating Scale (SRS), Extubation Conditions and Postoperative Conditions Following Reversal With Sugammadex
The purpose of this study is to study the effect of variations in the arterial CO2 concentration during deep neuromuscular block on the surgical conditions as assessed by the surgical rating scale
Read the detailed description
Surgical conditions in laparoscopic surgery are largely determined by the depth of neuromuscular relaxation during surgery. This is especially true in procedures which are confined to a narrow working field such as retroperitoneal laparoscopic surgery (eg. renal and prostatic surgery). In the previous study (BLISS study) deep neuromuscular block (NMB) has shown to provide superior surgical conditions compared to moderate NMB. Moreover, rapid reversal of a deep NMB at the end of surgery was possible with Sugammadex (4mg/kg). The deep NMB did not lead to any delay in extubation time and did not cause any prolongation of stay in the recovery room when the block was reversed with Sugammadex
Rapid, safe and complete reversal of profound NMB blockade was not possible until the discovery of Sugammadex. Sugammadex is a modified γ-cyclodextrin. It was developed to selectively bind free plasma rocuronium, a non-depolarizing steroidal neuromuscular blocking agent. The BLISS study was the first study in which the effect of deep NMB on surgical conditions was assessed. Surgical conditions in this study were scored by one surgeon on a newly applied surgical rating scale which ranges from one to five.
Although the BLISS study showed that a deep NMB provided better surgical conditions than a moderately deep NMB overall, there was a high variability in surgical rating scores. More over, even at the deep NMB, SRS scores of 3 (moderate, but acceptable conditions) were noted. This indicates that surgical conditions are influenced by other factors as well. Involuntary movement of the diaphragm is possibly such a major disturbant of the surgical field. Previous studies have shown a relative resistance to neuromuscular blocking agents of the diaphragm compared to the musclus adductor pollicis on which neuromuscular block is generally monitored. Hence contractions of the diaphragm may occure despite a deep NMB. This may be due to (high) arterial carbon dioxide (CO2) concentrations, which stimulate the respiratory neuronal pool in the brainstem and consequently activate the phrenic nerve. In normal circumstances, the respiratory centers try to maintain an arterial CO2 pressure of 40 mmHg. With intentional hyperventilation, the arterial CO2 pressure may be lowered to 10-20 mmHg. A low arterial CO2 pressure diminishes the respiratory drive and consequently phrenic nerve activity. This is supported by previous observations which showed increased abdominal muscle relaxation produced by hyperventilation. We therefore designed this study to evaluate the effect of arterial CO2 variation with concurrent deep NMB on the surgical conditions. Arterial CO2 tensions may be altered by adjusting the ventilator settings. Eg. by increasing minute ventilation volume, arterial CO2 concentration will lower. Regular arterial blood samples will be drawn to monitor arterial CO2 concentration.
We hypothesize that a Deep NMB combined with hypocapnia will result in a significant improvement of surgical conditions as rated on the surgical rating scale by one surgeon compared to deep NMB and normocapnia
Additional secondary end-points of the study include the effect of arterial CO2 variation on:
- economic parameters (time to spontaneous breathing, time to extubation, duration of surgery, and time in the post-anesthesia care unit)
- perioperative hemodynamics, abdominal pressure
- postoperative conditions (respiratory conditions, hemodynamics, arterial oxygen saturation, pain, sedation, nausea and vomiting)
- To assess the ability of anesthesiologists and surgeons to rate the surgical field using video snippets of the surgical field.
- Conditions
- Prostate Cancer, Renal Cancer
- Being tested
- hypocapnia, normocapnia
- Medical subject headings
- Prostatic Neoplasms, Kidney Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
hypocapniaOther
Also called Low CO2
Hyperventilation to the level of hypocapnia
normocapniaOther
Also called normal CO2
Normal ventilation to the level of nromocapnia
| Study group | Role | What they receive |
|---|---|---|
| hypocapnia | Experimental | arterial pCO2 of 3.5 kPa Receives: Other: hypocapnia |
| normocapnia | Active comparator | arterial PCO2 of 6.5-7.0 kPa Receives: Other: normocapnia |
What is being measured
The primary outcome is the main question the study is designed to answer.
Surgical Rating Scale
During a procedure, the surgical condition will be scored by one surgeon using a 5-point surgical rating scale. The rating scale is a 5-point ordinal scale ranging from 1 = poor condition to 5 = optimal surgical conditions. The surgeon will score the condition at 15 minute intervals.The values given on the surgical rating scale are averaged and the average value is used in the data analysis.
Measured: Peroperative
Secondary outcomes (6)
Hemodynamics
Hemodynamic conditions are studied during low arterial CO2 concentration and normal arterial CO2 concentration. The average of the measured mean arterial pressures at 15 minute intervals during anesthesia are presented
Measured: peroperative
Respiratory Function
The effect of low versus normal pCO2 concentrations on the postoperative respiratory function will be studied. Postoperative saturations are obtained at 15 minutes intervals. The data are averaged over time.
Measured: from the end of surgery untill 2 hours postoperative
Pain Intensity on an 11-point Scale in the Postoperative Period
The effect of low versus normal pCO2 concentrations on postoperative pain will be studied. Painscores are obtained at 15 minutes intervals and are expressed as a number on a 10 point scale (numeric rating scale; 1 (low)-10(maximum)). The data is avaraged over time
Measured: from the end of surgery untill 2 hours postoperative
Sedation
The effect of low versus normal pCO2 concentrations on postoperative sedation will be studied using the using the validated Leiden Observer's Assessment of Alertness/Sedation (0 (awake) - 6 (unarousable)) scale at 15 min intervals. The data are averaged over time.
Measured: from the end of surgery untill 2 hours postoperative
Nausea
The effect of low versus normal pCO2 concentrations on the incidence of postoperative nausea will be studied. The incidence is expressed as the percentage of people experiencing nausea per arm.
Measured: from the end of surgery untill 2 hours postoperative
Vomiting
The effect of low versus normal pCO2 concentrations on the incidence of postoperative vomiting will be studied. The incidence of vomiting is expressed as a precentage of the patients per arm.
Measured: from the end of surgery untill 2 hours postoperative
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Oct 2013 (estimated)
- Study startFeb 2014
- Primary completionOct 2015
- Study completionOct 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Prostate CancerStudies of the same condition, open and under way.
- More trials run by Leiden University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Care provider, Investigator, Outcomes assessor
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Leiden University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Principal investigator, Albert Dahan, Leiden University Medical Center
- Investigators
- Albert Dahan, MD, Principal investigator, LUMC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01968447
- Sponsor's protocol ID
- NL45461.058.13
- Acronym
- BLISSS2
- Status last verified
- Feb 2020
- First submitted
- 7 Oct 2013
- Last updated
- 16 Mar 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Publications
Boon M, Martini C, Hellinga M, Bevers R, Aarts L, Dahan A. Influence of variations in arterial PCO2 on surgical conditions during laparoscopic retroperitoneal surgery. Br J Anaesth. 2016 Jul;117(1):59-65. doi: 10.1093/bja/aew114. Epub 2016 May 6.
PubMed 27154574
Study at a glance
From the registry record, last updated by the sponsor on 16 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Deep Neuromuscular Block and Variations in Arterial PCO2 on the Surgical Rating Scale (SRS), Extubation Conditions and Postoperative Conditions Following Reversal With Sugammadex
- ClinicalTrials.gov ID
- NCT01968447
- Acronym / sponsor ID
- BLISSS2 / NL45461.058.13
- Conditions
- Prostate Cancer, Renal Cancer
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Leiden University Medical CenterUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- Feb 2014
- Primary completion
- Oct 2015 (actual)
- Study completion
- Oct 2015 (actual)
- First posted
- 24 Oct 2013 (estimated)
- Results
- Posted 16 Mar 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to study the effect of variations in the arterial CO2 concentration during deep neuromuscular block on the surgical conditions as assessed by the surgical rating scale
Detailed description
Surgical conditions in laparoscopic surgery are largely determined by the depth of neuromuscular relaxation during surgery. This is especially true in procedures which are confined to a narrow working field such as retroperitoneal laparoscopic surgery (eg. renal and prostatic surgery). In the previous study (BLISS study) deep neuromuscular block (NMB) has shown to provide superior surgical conditions compared to moderate NMB. Moreover, rapid reversal of a deep NMB at the end of surgery was possible with Sugammadex (4mg/kg). The deep NMB did not lead to any delay in extubation time and did not cause any prolongation of stay in the recovery room when the block was reversed with Sugammadex
Rapid, safe and complete reversal of profound NMB blockade was not possible until the discovery of Sugammadex. Sugammadex is a modified γ-cyclodextrin. It was developed to selectively bind free plasma rocuronium, a non-depolarizing steroidal neuromuscular blocking agent. The BLISS study was the first study in which the effect of deep NMB on surgical conditions was assessed. Surgical conditions in this study were scored by one surgeon on a newly applied surgical rating scale which ranges from one to five.
Although the BLISS study showed that a deep NMB provided better surgical conditions than a moderately deep NMB overall, there was a high variability in surgical rating scores. More over, even at the deep NMB, SRS scores of 3 (moderate, but acceptable conditions) were noted. This indicates that surgical conditions are influenced by other factors as well. Involuntary movement of the diaphragm is possibly such a major disturbant of the surgical field. Previous studies have shown a relative resistance to neuromuscular blocking agents of the diaphragm compared to the musclus adductor pollicis on which neuromuscular block is generally monitored. Hence contractions of the diaphragm may occure despite a deep NMB. This may be due to (high) arterial carbon dioxide (CO2) concentrations, which stimulate the respiratory neuronal pool in the brainstem and consequently activate the phrenic nerve. In normal circumstances, the respiratory centers try to maintain an arterial CO2 pressure of 40 mmHg. With intentional hyperventilation, the arterial CO2 pressure may be lowered to 10-20 mmHg. A low arterial CO2 pressure diminishes the respiratory drive and consequently phrenic nerve activity. This is supported by previous observations which showed increased abdominal muscle relaxation produced by hyperventilation. We therefore designed this study to evaluate the effect of arterial CO2 variation with concurrent deep NMB on the surgical conditions. Arterial CO2 tensions may be altered by adjusting the ventilator settings. Eg. by increasing minute ventilation volume, arterial CO2 concentration will lower. Regular arterial blood samples will be drawn to monitor arterial CO2 concentration.
We hypothesize that a Deep NMB combined with hypocapnia will result in a significant improvement of surgical conditions as rated on the surgical rating scale by one surgeon compared to deep NMB and normocapnia
Additional secondary end-points of the study include the effect of arterial CO2 variation on:
- economic parameters (time to spontaneous breathing, time to extubation, duration of surgery, and time in the post-anesthesia care unit)
- perioperative hemodynamics, abdominal pressure
- postoperative conditions (respiratory conditions, hemodynamics, arterial oxygen saturation, pain, sedation, nausea and vomiting)
- To assess the ability of anesthesiologists and surgeons to rate the surgical field using video snippets of the surgical field.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| hypocapnia | Experimental | Other: hypocapniaarterial pCO2 of 3.5 kPa |
| normocapnia | Active comparator | Other: normocapniaarterial PCO2 of 6.5-7.0 kPa |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- (i) Patients diagnosed with renal or prostatic disease who are will undergo an elective laparoscopic renal surgical procedure or laparoscopic prostatectomy;
- (ii) ASA class I-III
- (iii) > 18 years of age;
- (iv) Ability to give oral and written informed consent.
Key exclusion criteria (9 listed)
- (i) Known or suspected neuromuscular disorders impairing neuromuscular function;
- (ii) Allergies to muscle relaxants, anesthetics or narcotics;
- (iii) A (family) history of malignant hyperthermia;
- (iv) Women who are or may be pregnant or are currently breast feeding;
- (v) Renal insufficiency, as defined by serum creatinine x 2 of normal, or urine output < 0.5 ml/kg/h for at least 6 h. When available, other indices will be taken into account as well such as glomerular filtration rate < 60 ml/h and proteinuria (a ratio of 30 mg albumin to 1 g of creatinine).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| hypocapniaAlso: Low CO2Hyperventilation to the level of hypocapnia | Other | hypocapnia |
| normocapniaAlso: normal CO2Normal ventilation to the level of nromocapnia | Other | normocapnia |
Primary outcome
Surgical Rating Scale
Time frame: Peroperative
During a procedure, the surgical condition will be scored by one surgeon using a 5-point surgical rating scale. The rating scale is a 5-point ordinal scale ranging from 1 = poor condition to 5 = optimal surgical conditions. The surgeon will score the condition at 15 minute intervals.The values given on the surgical rating scale are averaged and the average value is used in the data analysis.
6 secondary outcomes
Hemodynamics
Time frame: peroperative
Respiratory Function
Time frame: from the end of surgery untill 2 hours postoperative
Pain Intensity on an 11-point Scale in the Postoperative Period
Time frame: from the end of surgery untill 2 hours postoperative
Sedation
Time frame: from the end of surgery untill 2 hours postoperative
Nausea
Time frame: from the end of surgery untill 2 hours postoperative
Vomiting
Time frame: from the end of surgery untill 2 hours postoperative
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Mar 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 27154574Boon M, Martini C, Hellinga M, Bevers R, Aarts L, Dahan A. Influence of variations in arterial PCO2 on surgical conditions during laparoscopic retroperitoneal surgery. Br J Anaesth. 2016 Jul;117(1):59-65. doi: 10.1093/bja/aew114. Epub 2016 May 6.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Albert Dahan, MD principal investigator
LUMC
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing hypocapnia and normocapnia in people with Prostate Cancer and Renal Cancer, run by Leiden University Medical Center at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 16 Mar 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Surgical Rating Scale (time frame: Peroperative). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01968447, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Mar 2020.