Incidence of Postoperative Delirium in Cancer Patients After Laparoscopic Surgery in Trendelenburg Position

Comparison of Two Different Anesthetic Techniques on Incidence of Postoperative Delirium in Cancer Patients After Laparoscopic Surgery in Trendelenburg Position: A Prospective Randomized Clinical Trial

Postoperative delirium is an acute mental syndrome that is caused by diffuse cerebral dysfunction resulting from the action of predisposing and precipitating factors acting together. It is associated with an increase in mortality and postoperative morbidity and prolongs the period of hospitalization of the patient Videolaparoscopic surgery has been increasingly used as a therapeutic and diagnostic method. In order to have a good visualization of the anatomical structures on which it will act, it is necessary to introduce gas into the cavity, a mandatory component known as pneumoperitoneum. This technique gives special characteristics for the conduction of anesthesia, since the positive intra-abdominal pressure results in changes in the patient's physiology. Some types of laparoscopic surgery require the position of Trendelenburg for better visualization of the operative field. Among the changes related to this position are the increase in cardiac output and intracranial pressure.

In order to optimize the anesthetic procedure, anesthetic blocks have been increasingly used, especially the spinal. The association of general anesthesia with spinal anesthesia, followed by its contraindications is advantageous, because lower doses of anesthetic agents are necessary for the maintenance of general anesthesia. This association results in an earlier awakening, a reduction of nausea / vomiting, postoperative pain, length of hospital stay, cost effectiveness and greater patient satisfaction. As a disadvantage, by associating general anesthesia with spinal anesthesia, patients become susceptible to the adverse events of spinal anesthesia. Among these, the most common are headache, hypotension, nausea and vomiting, pruritus, urinary retention and tremor. Performing spinal anesthesia with opioids alone, without the use of local anesthetic is also possible, with morphine being the most used. The benefit of this variation of technique is analgesia for a period of 12 to 24 hours, without the cardiovascular consequences resulting from the action of the local anesthetic.

JUSTIFICATION: There are no studies in the literature evaluating The objective of this study is to analyze if the anesthetic techniques employed, general anesthesia or general anesthesia associated with subarachnoid block, for videolaparoscopic oncologic surgeries, in Trendelenburg position, differ in relation to the incidence of delirium in the postoperative period.

Patients will be allocated sequentially in 2 groups. Sequential allocation will be used in order to control age as a possible confounding factor for the outcome of interest.

These patients will be monitored intraoperatively with electrocardiogram (ECG), noninvasive pressure, pulse oximetry, capnography, BIS, monitor of neuromuscular blocker (TOF), esophageal temperature and Trendelenburg angle.

The measured moments will be patient entry in the operating room, after pre-anesthetic medication, anesthetic pre-induction, after anesthetic induction, after surgical incision, after pneumoperitoneum infusion, after Trendelenburg position, every 15 minutes until the end of the procedure and after extubation.

All patients will receive morphine 50 mcg via the spinal route. All patients will receive intravenous pre-anesthetic medication midazolam 0.03 mg / kg for comfort during spinal anesthesia and 500 ml of crystalloid solution prior to blockade associated with 4 ml / kg / hour of crystalloid solution plus volume to be depended of clinical parameters.

Subarachnoid block will be performed in the seated position, antisepsis / asepsis with alcoholic chlorhexidine, location of the L3 / L4 space, needle puncture with whitacre 27 G, barbotation of 0.5 ml and injection lasting 5 to 7 seconds.

Spinal morphine will be performed with the same anesthetic technique described in the subarachnoid block.

A general anesthetic with pre-oxygenation 8 liters / minute for 5 minutes + fentanyl 3 mcg / kg + propofol 2 mg / kg + rocuronium 0.6 mg / kg will be performed. Patients will be ventilated with a mixture of oxygen and air through an inspired fraction of 40% oxygen and maintaining an expired concentration of carbon dioxide between 35 and 45 mmHg. Anesthesia will be maintained with remifentanil (ng / ml) through Minto's pharmacokinetic model (BBraun infusion syringe - Perfusor® Space model) and desflurane (Fe%).

Hypnosis will be guided by maintaining BIS between 40 and 60 and the dose of remifentanil will be adjusted by vital signs.

Patients with medium arterial pressure with values lower than 60 mmHg will be medicated with vasopressors depending on heart rate. If heart rate is greater than 60 beats per minute (bpm) metaraminol 0.5 mg will be used and 5 mg ephedrine will be used if heart rate less than 60 bpm.

In both groups, the patients will be kept warm with a thermal blanket and will have their esophageal temperature measured (40 cm from the incisor teeth).

After the surgical procedure, neuromuscular blockade will be antagonized with suggamadex, according to the monitoring of neuromuscular blockade through TOF.

• Deep block (at least 1 to 2 responses in PTC, but prior to the appearance of T2, ie the second response to TOF): 4 mg / kg.
• Moderate block (after onset of T2): 2mg / kg.
• 16 mg / kg is recommended if there is a clinical condition requiring rapid reversal (approximately 3 minutes) following the single dose of rocuronium at 1.2 mg / kg.

After 5 minutes of extubation, vital signs (blood pressure, heart rate, saturation) will be collected and the patient will be evaluated for the presence of delirium. Dipyrone 2 grams and parecoxib 40 mg will be performed without contraindication for postoperative analgesia.

Patients will then be referred to the anesthetic recovery room, where they will continue to be monitored with ECG, noninvasive pressure and pulse oximeters. They will also be evaluated for pain in the numerical estimate scale (NRS) (0 = no pain, up to 10 = maximum pain), on arrival and every 30 minutes until the time of discharge into the room. Those who present pain with NRS greater than 4 in PACU will be treated with morphine 1 mg every 10 minutes. Those with nausea / vomiting will be given alizapride 50 mg.

Patients will be assessed with regard to the appearance of delirium by means of CAM (Confusion Assemption Method) in association with the Richmond Agitation Sedation Scale (RASS) scale.

CAM is a simple screening method based on the following four questions, with Criteria 1 and 2 plus 3 or 4 being present:

1. Acute onset: Is there evidence of acute change in the patient's underlying mental state?
2. Attention Disorder: Has the patient had difficulty focusing on his or her attention, for example, was easily distracted or had difficulty following what was being said?
3. Disorganized thinking: Was the patient's thinking disorganized or incoherent, with dispersive or irrelevant conversion, unclear or illogical flow of ideas, or unpredictable change of subject?
4. Changes in level of consciousness: Does the patient present altered level of consciousness such as lethargy, torporous, comatose? The RASS, was developed with the purpose of characterizing the level of consciousness and agitation. Signs of hyperactive delirium are defined as scores ranging from +1 (anxious patient), +2 (frequent uncoordinated unintentional movements, fight against ventilation), +3 (aggressive) to +4 (very aggressive). Signs of hypoactive delirium are defined as RASS ranging from - 5 (patient does not respond), - 4 (no response to voice sound), -3 (movements or ocular opening to voice sound), -2 (awakens briefly), - 1 (not completely alert) to 0 (patient calm or sleepy).

This evaluation will be performed by nurses, previously trained, on arrival at PACU every 30 minutes until discharge from the post-anesthetic recovery room and 24 hours after the patient's discharge from the hospital. In cases where the patient has an episode of persistent delirium for more than 1 hour, the evaluation of a psychiatrist will be requested for follow-up and treatment.

Inclusion Criteria:

• Oncologic patients submitted to elective videolaparoscopic surgery in Trendelenburg position
• 18 years or older
• ASA lesser than 3
• period of at least 2 hours in Trendelenburg position

Exclusion Criteria:

• With absolute contraindication and related to spinal anesthesia
• With difficult airway prediction with possibility of awake intubation.
• With previous diagnosis of: cognitive disorder and / or depression.
• Chronic use of benzodiazepines (use during the last 12 weeks).
• Referred to perform the postoperative ICU.
• With diagnosis of anemia (Hemoglobin <10).
• With diagnosis of current infection.
• With renal disease with stage> G3a (glomerular filtration rate <45 ml / min / 1.73 m2.
• With body mass index (BMI) characterized by obesity (BMI> 30 kg / m2).
• With history of nausea / vomiting in previous anesthetic procedures.
• With diagnosis of malignant hyperthermia.