This project has 2 phases. Phase 1: diagnostic test study, to evaluate the efficacy of the variation of pupillary size (PDR) to detect pain in ICU patients regarding to Behavioural Pain Scale (BPS) and ESCID (Conductual Scale Pain Index). Phase 2: controlled and aleatorized clinical trial to evaluate efficacy in PDR monitoring after painful assessed minimum stimulus with the best diagnostic efficiency on phase 1, as a need of analgesia indicator tool.

The sample will be patients over 18 years, sedated and mechanically ventilated, with an initial BPS of 3, RASS between -1 and -4, not able not to communicate , with inform consent signed. Exclusion criteria will be: ophtalmologic pathology and administration of drugs interfering pupillary reflexes. Measurements before/during pain/non-pain situations, aspiration of secretions and calibrated intensity stimulus through the pupilometer Algiscan. The investigators will study association between pain according to BPS/ESCID and pupillary dilatation according to pupillometry and percentage of patients with pain and preanalgesia according to pupillometry and standard clinical practice.

Inclusion Criteria:

• Patients over 18 years.
• Analgosedated patients under mechanical ventilation.
• Unable to communicate (verbal or motor).
• Patients with initial BPS of 3, and RASS from -1 to -4.
• Familiar prior informed consent.

Exclusion Criteria:

• Patients treated with muscle relaxants.
• Severe Critical Polyneuropathy.
• Pupillary reflex affectation in diabetic patients (diabetic papillopathy,glaucomatous optic neuropathy) or any other pathologies like Adie´s Syndrome, Argyl-Robertson pupil.
• Patients with tansmisible ocular infections.
• Patients with possible injury of the third carnial nerve (Horner´s syndrome) due to injury to the brainstem, cervical cord, cancer of the upper lobe the lung, dissection of the carotid and/or cluster headache.
• Acute cerbrovascular conditions with Glasgow Coma Scale less than 6, or increased intracranial pressure, or pontine base infarction.
• Drugs that interfere with the pupillary reflex (clonidine, dexmedetomidine, metoclopramide, tramadol, droperidol, ketamine, nitrous oxide).
• Patients under metoclopramide, if given 10 minutes prior the measurement of the pupillary reflex (PDR).
• Patients during the first 24 hours after Cardiac Arrest (CRP).
• Severe unestable comorbidity with doses of norepinephrine> 0.6 microg/kg/min and/or dobutamine>10 microg/kg/min or drenalin any doses.
• Patients with untreated pheochromocytomas.
• Refuse to participate in the trial.