Innovative Sedative Strategies


This piece of research started in 2011 thanks to a financing of Regione Lombardia for the Independent Research. It consists of 4 different Work Packages (WP1); the first one (WP1) includes 14 Italian and Swiss centers (see map), the second (WP2) carries out exclusively to the Ospedale San Paolo in Milan, and the last two (WP3 and WP4) concern the 7 hospitals Milan area already involved in WP1.


Enteral Sedation and Intravenous Sedation in High-Risk Patient (WP1)

Anxiety and agitation are frequent events in critical patients that are often triggered by multifactorial causes; besides organic origin such as hypoxaemia, hypoglycaemia, pain or abstinence from drugs, other conditions can led to them: frequent and unexpected stimulations, invasive procedures, deprivation of sleep, the supine obliged position,the continuous presence of noises and artificial light and the impossibility to communicate with the staff. Therefore adequate levels of sedation represent a main goal in the treatment of the crtitical patient since they allow the staff to perform the necessary diagnostic and therapeutic invasive maneuvers, assuring an adequate comfort to the patient and reducing the risk of invasivities self-removal (tubes, drains, catheters etc).

In the last few years there has been a progressive increase in scientific papers regarding sedation in critical patients. The prevailing trends emerging from international literature indicates the opportunity to put sedation target at a lower level compared to the past, because sedative therapy has a lot of potential negative effects on hemodynamic, respiratory weaning process and lenght of the stay in ICU. Last but not least is the economic matter, because of the high cost of sedative drugs used in these patients.

Since today the intravenous route has been universally used for administration of sedative drugs. Recent studies have demonstrated that the gastroenteric tract is functional and suitable , regarding drugs absorption and nutritional purposes, in the overwhelming majority of the cases, also in extremely compromised clinical scenarios and even in the early phases of ICU stay. We have published two papers in wich we studied the feasibility and the efficacy of the enteral sedation by administrating hydroxyzine (antagonist H1 receptor) and lorazepam (benzodiazepine). In these studies we have demonstrated that the sole enteral sedation is feasible and efficacy when the sedation target is to have a calm, awake and cooperative patient, including periods of physiological sleep. Moreover, enteral sedation allows to obtain remarkable advantages in terms of hemodynamic stability, minimize the interference in the weaning process and permits a significative reduction of costs in comparison with the intravenous approach.



Pharmacokinetics of Melatonin (WP2)

In order to restore the sleep-wake cycle, scientific studies have been carried out on the uselfullness of Melatonin in critically ill patients; currently Melatonin is administered orally via tablets, but recently new systems for administrations have been developed incorporating Melatonin into lipid nanoparticles for transdermal adsorption through patches, with prolongation of plasmatic half life. The study therefore aims to evaluate the pharmacokinetics of transdermal Melatonin and its redox effect compared to enteral administered Melatonin.

Training Program for Operators on validated instruments (WP3)

International guidelined state that in Intensive Care Units (ICU) there must be a systematically assessment of pain, the state of consciousness and acute brain dysfunction and appropriate assessment must be made through the use of validate scales such as: Verbal Numeric Rating (VNR) or the Beavioral Pain Scale (BPS) – for the monitoring of pain – the Richmond Agitation Sedation Score (RASS) – to assess the state of conscioussness – the Confusion Assessment Method for Intensive Care Unit (CAM-ICU) – for the detection of acute brain dysfunction.

The need to use validated scales arises from the need to constantly balance the amount and timing of administration of sedative drugs. These are needed to control the sedation of critically ill patients from stress and to provide the necessary adaptation of the patient to invasives procedures; the appropriate use of sedative drugs allows the reduction of mechanical ventilation and a minor impact of drugs on the cardiovascular and respiratory system.

Although the international guidelines prescribe the use of all the three scales it is always difficult to implement their enployement in the medical and nursing staff. Even if the time to perform these test is short, the necessity to carry out a process of learning specifically planned represents a not negligible obstacle. The necessity to promote an adequate formation on the use of the scales is supported by the data on scientific literature that suggest a correct evaluation of the neurological state would afford the medical staff to titrate the administration of sedative drugs, diminishing mortality and morbility. The right use of RASS and CAM-ICU scales meaningfully reduced the lacked diagnosis of delirium.

Purpose of the study

Evaluate the effectiveness of a training program for medical and nursing staff on the application of BPS scale, RASS and CAM-ICU in order to ensue that every high risk patient is continously monitored. This evaluation will be obtained by the comparison between groups of doctors and nurses who have received a training course with different pedagogical strategies and groups that will benefit from the same training at a later time.

The hyphotesis concerned for this study is to obtain an assessment of patients neurological parameters with validated instruments increased by 30% compared to pre-training observational period.

Secondary objectives include:

  1. The detection of difficulties reported by the nursing staff in the application of the scales.
  2. Assessement of medical and nursing workload related to the performance of BPS, RASS and CAM-ICU.
  3. An increased awarness of the importance of the use of scales in terms of benefits for the patient in order to realistically assess the relationship between costs (time spent in the administration of the scales) and benefits (clinical and economic outcomes) in the detection of pain, state of cosciousness and delirium.
  4. Mantaining the effectiveness of training over time measuring the extinction one year later.


Post Traumatic Disorder Stress (PTSD) following hospitalization in ICU (WP4)

Patients discharged from ICU may develop physical and psychological symptoms in a moment following the discharge as they perceived the intensive therapy as a traumatic event. Some studies have shown that the duration of sedation and the use of a sedation protocol affect the long term psychological outcome: daily interruption of sedation, duration of sedation and depth of sedation may interfere with the development of PTSD.

The main purpouse of this research project is to evaluate the efficacy of the enteral route of drugs administration compared to the intravenous one to obtain the desired level of sedation and to check whether the maintenance of conscious sedation results in a lower prevalence of PTSD because of the constant possibility to gain real memories.

chi siamo_i nostri progetti_strategie sedative innovative

In Terapia Intensiva collaborano molte persone con ruoli diversi. Solo grazie al contributo di tutti, pazienti compresi, si possono raggiungere risultati eccellenti.

Link veloci

Gestire il dolore

ico-flowchartdoloreFlowchart dolore

Gestire la sedazione

ico-flowchart-sedaz-agitFlowchart sedaz/agitaz

Gestire il delirium

ico-flowchart-deliriumFlowchart Delirium
ico-manuale-cam-icuManuale CAM-ICU
ico-schedalavoro-cam-icuScheda di lavoro CAM-ICU


Questo sito è stato realizzato grazie al contributo di:


Finanziamento per la Ricerca Indipendente
(Decreto DGS 13456 del 22 dicembre 2010)

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