250ml fluid challenges with a recommended solution as required in order to achieve a maximal value of stroke volume. The absence of fluid responsiveness will be defined as the absence of a sustained rise in stroke volume of at least 10% for 20 minutes or more. In addition, patients will receive a low dose inotrope infusion at a fixed rate which will be commenced after fluid replacement has been initiated. The choice of inotrope will be made at the discretion of the local investigator, according to local preference and availability. The options are dobutamine at a dose/rate of 2.5 µg/kg/min and dopexamine at an equipotent dose/rate of 0.5 µg/kg/min. The infusion rate will be reduced and/or discontinued if the patient develops a tachycardia (heart rate greater than 100bpm) for more than 30 minutes despite adequate anaesthesia and analgesia. Data collection and follow-up for such patients will be performed as normal. All other management decisions will be taken by clinical staff. care group Patients in the control group will be managed by clinical staff according to usual practice. This will include 250ml fluid challenges with a recommended intra-venous fluid (see SOP for the management of control group patients) administered at the discretion of the clinician guided by pulse rate, arterial pressure, urine output, temperature gradient, serum lactate and base excess. If a specific haemodynamic end-point for fluid challenges is to be used, the most appropriate would usually be a sustained rise in central venous pressure of at least 2 mmHg for 20 minutes or more. Patients should not be randomised if the clinician intends to use cardiac output monitoring regardless of study group allocation; this is considered refusal’ and is a specific exclusion criteria. However, clinical staff ‘clinician are free to request cardiac output monitoring if this is required to inform the treatment of a patient who becomes critically ill (e.g. because of severe haemorrhage) during the trial intervention period. In this situation a protocol deviation form will be completed. 7.5 Intervention algorithm 7.6 Blinding and procedures to minimise bias OPTIMISE II is a pragmatic trial of a treatment algorithm. It is not possible to conceal treatment allocation from all staff in trials of this type. Therefore, this trial will be
250ml fluid challenges with a recommended solution as required in order to achieve a maximal value of stroke volume. The absence of fluid responsiveness will be defined as the absence of a sustained rise in stroke volume of at least 10% for 20 minutes or more. In addition, patients will receive a low dose inotrope infusion at a fixed rate which will be commenced after fluid replacement has been initiated. The choice of inotrope will be made at the discretion of the local investigator, according to local preference and availability. The options are dobutamine at a dose/rate of 2.5 µg/kg/min and dopexamine at an equipotent dose/rate of 0.5 µg/kg/min. The infusion rate will be reduced and/or discontinued if the patient develops a tachycardia (heart rate greater than 100bpm) for more than 30 minutes despite adequate anaesthesia and analgesia. Data collection and follow-up for such patients will be performed as normal. All other management decisions will be taken by clinical staff. care group Patients in the control group will be managed by clinical staff according to usual practice. This will include 250ml fluid challenges with a recommended intra-venous fluid (see SOP for the management of control group patients) administered at the discretion of the clinician guided by pulse rate, arterial pressure, urine output, temperature gradient, serum lactate and base excess. If a specific haemodynamic end-point for fluid challenges is to be used, the most appropriate would usually be a sustained rise in central venous pressure of at least 2 mmHg for 20 minutes or more. Patients should not be randomised if the clinician intends to use cardiac output monitoring regardless of study group allocation; this is considered ‘clinician refusal’ and is a specific exclusion criteria. However, clinical staff are free to request cardiac output monitoring if this is required to inform the treatment of a patient who becomes critically ill (e.g. because of severe haemorrhage) during the trial intervention period. In this situation a protocol deviation form will be completed. 7.5 Intervention algorithm 7.6 Blinding and procedures to minimise bias OPTIMISE II is a pragmatic trial of a treatment algorithm. It is not possible to conceal treatment allocation from all staff in trials of this type. Therefore, this trial will be
OPTIMISE%20II%20Protocol%20v1.0%2002.11.2016.docx