BACKGROUND:As the potentiality of deceased organ donation mostly depends on the number of brain deaths (BDs), the aim of this study is to quantify rates and probabilities of BD declaration in Italy.METHODS:Deaths with acute cerebral lesion (ACLDs) in the Italian ICUs have been prospectively collected. A total of 27,490 ACDLs occurred in 5 years. Age, gender, etiology, timing of death and ICU Region have been utilized for multivariate analysis.RESULTS:The global ratio of BD declarations to ACLDs was 39.9%. The rates of ACLDs, BD declarations and actual donors were 93.5, 37.3 and 19.7 pmp respectively. Wide variability resulted among Regions, with 148.2 ACLDs, 77.8 BD declarations and 42 donors pmp as benchmark. The probability of being BD declared was significantly higher in stroke compared with head injury (OR 1.6, P<0.001) and in females (OR 1.5, P<0.001), with half the Regions missing around 50% of BD declarations compared with the benchmark, particularly in elderly patients.CONCLUSION:Predictable factors associated with BD declaration can be identified in ACLD management. Positive factors leading to the identification of potential organ donors, i.e., the capacity of declaring BD in all the patients fulfilling BD criteria irrespective of age and etiology, could be captured in the best performing regions and reproduced throughout the Country. The implementation of simple indicators based on prospective ACLD monitoring, i.e. the declared BDs to ACLDs in ICU ratio, may be helpful in achieving efficiency targets and reliable comparisons of outcomes in the identification of BD potential organ donors.

For circulatory death Italian legislation provides that death declaration has to be performed only after irreversible cardiac arrest, i.e. by 20-minute flat electrocardiogram. This 20-minute no-touch period discouraged over the years Italian physicians to transplant organs from non-heart-beating donors/donation (NHBD). However, several experimental works demonstrated kidney viability even after 40-minute acirculatory warm ischemia. These results prompted the Pavia's transplantation group to establish the first NHBD programme in Italy: the “Programma Alba”. All details and related preliminary results have been recently published [1]. According to our experience on uncontrolled donors treated with post-mortem Extra Corporeal Membrane Oxygenation (ECMO) a category VI might be added to usually reported classification of NHBD/DCD (Donation after Cardiac/Circulatory Death). Description for such partially controlled category VI is: Death during ECMO maintenance [1]. In such case of organ donation death can be determined by brain [1,2] or cardiac/circulatory criteria according to ethical and legal frameworks. These donors are initially NHBD and, if neurological criteria are applied, become DBD (Donors after Brain-Death), i.e. organ perfusion has initially been absent and then ECMO maintained. These NHBD donor organs suffer from acirculatory warm ischemic insult due to different reasons: a) immediately after the initial cardiac arrest and before CPR if death is declared by neurological criteria; b) before CPR and during the no-touch period if cardiac criteria are used; c) in both cases organ perfusion may be suboptimal during the ECMO prolonged artificial circulation. If neurological criteria are used, organs might be considered like those from DBD/HBD (Heart-Beating Donor), but their perfusion is artificial as for uncontrolled DCD, eventually misleading the transplant team decisions. In Pavia 6 successful kidney transplants have been performed with 3 DCD and 2 DBD category VI non-heart-beating donors. Kidneys from ECMO-NHBD DBD donors suffered from a severe acute tubular necrosis similar to the damage caused by ischemia in Maastricht II and in ECMO-NHBD DCD donors. In conclusion, a simple but clinically relevant new classification of donors based on organ perfusion and including prior-to-death ECMO is proposed: Type I, when organ perfusion is natural even if supported by drugs; the type I category includes HBD/DBD. Type II, when cardiac/circulatory perfusion is absent or obtained by external artificial devices before organ retrieval. The type II category includes NHBD both DCD and DBD. To enhance information on the quality of the graft, two simple acronyms including all donation categories are suggested: 1) DDNP type I (Deceased Donor with Natural Perfusion) 2) DDAP type II (Deceased Donor with Artificial or Absent Perfusion).

Excellent results of organ transplantation have caused an enormous increase in the number of patients awaiting for such treatment. Organ recovery rate from deceased donors in European Countries in 2010 ranged from 2.7 p.m.p. in Bulgaria to 32 p.m.p. in Spain. Deceased donation rate p.m.p. in Italy and Poland amounted to 21.7 and 13.3 respectively. The reason of organ shortage is difficult to comprehend since significantly more patients die in intensive care units (ICUs) due to cerebral vascular events or head trauma. The aim of this study was to compare the potential of deceased organ donation with the real organ recovery rate in two European countries - Poland and Italy. The Italian Registry of Deaths with Acute Cerebral Lesion (DACL) in ICUs confirmed that BD declarations are consistently less than expected number. Over a 2-year period, BD declarations, i.e. potential DBD donors, were 43% of the 10,304 referred DACL. Considering 55% to 60% as possible benchmarking, approximately a 1000 BD declarations per year seem to be missing in Italy. The Italian law indicates that death must be determined by neurological criteria, regardless of potential organ donation, in all cases as soon as all the criteria of BD are completely fulfilled. All patients with neurological criteria of death, under mechanical ventilation in ICU, must be referred to the medical management of a hospital. Declaration of death by neurological criteria must be performed independently from potential organ donation and before any family interview about donation. Unfortunately, collected data suggest that many brain deaths are not declared in Italy (“silent BDs”): ICU doctors may wait for circulatory arrest under mechanical ventilation to avoid diagnostic procedures, excessive workload and BD explanations to the family. The data on missing donors (or “silent deaths”) in Poland are similar. In 2010, out of 55 000 patients treated In ICUs, 23,400 died. According to DOPKI donation index (EU) in approximately 3194 of these pts brain death could have been diagnosed. This translates into 1340 dead pts (42%), who could have been considered as potential donors. Regarding family refusal rate, logistic problems and medical contraindications (20%), organs could have been recovered from nearly 1100 deceased donors. In the same year, only 655 deceased pts were referred as potential donors and at least one organ was recovered and transplanted from 509 real donors. Conclusions: Clear and simple international guidelines should be defined and implemented by Scientific Societies and Health Authorities in all the European Countries to support intensivists in determining and declaring death by neurological criteria in all brain-dead patients and ensuring an immediate withdrawal of any treatment as soon as BD has been declared if organ donation is not planned. A universal death definition (and implementation) is needed, not only to increase organ recovery from deceased donors but mainly to meet clinical and ethical principles.

Rizzato, L.; Procaccio, F.; Ricci, A.; D'Alessandro, F.; De Cillia, C.; Lolli, F.; Venettoni, S.; Costa, Nanni A. Author Information

Brain death (BD) is not a stable, objective condition; in fact, it strongly depends on early intensive treatment before death, brain stem reflex testing, and intensive care unit (ICU) physician attitudes. Consequently, unpredictable "silent" BDs due to inadequate treatment or omitted declaration may affect potential organ donations. Several lines of evidence suggest that 55% to 65% of all deaths among patients with acute cerebral lesions (DACL) in the ICU may become brain deaths. Since DACL are easily measurable, deviations from the expected ratio of declarations will disclose "silent" BDs. Results from the National Registry of DACL in ICU settings have confirmed that BD declarations are consistently fewer than the number expected in Italy, particularly in regions where organ donation rates are low. Only 43% of the 10,304 referred DACL were potential donors in a 2-year period. Thus, around 1000 BDs per year are missing in Italy. Significant clinical factors for lost BDs may be older age and timing of death. As DACL represent the global donation potentiality (possible donors), we suggest the use of a new indicator-DACL in ICU per million population-and careful analyses of differences in DACL per million people among regions. In conclusion, since striking deviations from the expected ratio between BD declarations and deaths with an acute cerebral lesion exist in some regions, targeted training and support to ICUs should be planned. As adequate neurointensive treatment can improve outcomes and reduce "silent" BDs, more organ donors may exist where patients with acute cerebral lesion are better treated.

Cumulative evidence of potential benefits of electroencephalography (EEG) and evoked potentials in the management of patients with acute cerebral damage has been confirmed. Continuous EEG monitoring is the best method for detecting nonconvulsive seizures and is strongly recommended for the treatment of status epilepticus. Continuously displayed, validated quantitative EEG may facilitate early detection of secondary cerebral insults and may play a decision-making role in the management of patients with head injury, stroke, or subarachnoid hemorrhage. Long-latency auditory evoked potentials and cognitive components constitute a new field of interest for the progress of comatose patients. Motor evoked potentials may become clinically important both in acutely injured and elective postoperative patients. In the neurointensive care units adequate techniques can be selected to answer targeted clinical questions. The efficacy can be improved by implementing educational projects based on ad hoc training of nurses and neurointensive care specialists.

BACKGROUND:Nosocomial infection is one of the most common complications affecting patients admitted in intensive care units (ICU). The aim of this study is to evaluate rates of ICU-acquired infections, potential risk factors for these infections, causative microorganisms and antibiotic resistance patterns.METHODS:A 1-day point-prevalence study was conducted in 39 ICUs in Triveneto area (Italy) in November 1998. The overall study population included 188 patients with mean age of 61.4+/-19.3 years; the mean SAPS II score at entry into the ICU was 44.4+/-16.8 and the median duration of hospitalization was 9 days (range 2-636).RESULTS:A total of 59 patients (31.4%) had 79 episodes of ICU-acquired infections; pneumonia (45.5%), bloodstream infection (30.4%), and urinary tract infection (11.4%) were the most frequent types of infection. The leading causative microorganisms were S. aureus (24.4%, 77% of them were resistant to methicillin), Enterobacteriaceae (24.4%), P. aeruginosa (23.2%), fungi (12.2%), coagulase-negative staphylococci (7.3%) and Enterococcus spp (4.9%). Independent risk factors for nosocomial infections were duration of hospitalization >7 days (OR 4.29, 95% CI 1.82-10.1), SAPS II score >30 (OR 3.34, 95% CI 1.0-11.18), total parenteral nutrition (OR 2.69, 95% CI 1.19-6.07) and tracheostomy (OR 1.88, 95% CI 0.84-4.20).CONCLUSIONS:Nosocomial infections are relatively frequent in Triveneto area ICUs. The predominance of pneumonia and bloodstream infection, and the high frequency of antibiotic-resistant pathogens indicate that resources had to be assigned towards the implementation of control programs of those infections, monitoring of antibiotic resistance and prescription, and antibiotic therapy guidelines.

The number of deaths with acute cerebral lesion represents a sensible index and a key factor for evaluating the potential organ donor pool in small regions and in the single intensive care unit. Collected data demonstrate that in the Veneto Region the efficiency of solid organ retrieval can be improved and that organ donor shortage may depend, beyond family refusal, on clinical and cultural factors that hamper stabilized heart-beating deaths. Most potential donors with age over 70 or problematical clinical situations are preventively excluded by ICUs physicians. To improve organ donation all the patients who die in spite of neuro-intensive treatment should be prevented from circulatory arrest to permit legal declaration of death. Thus more potential organ donors without absolute contraindications could be recovered and time would exist for discussing any problematical situation with experts in organ procurement, particularly in respect to existing urgencies in the waiting list.

If pragmatic recommendations for treatment of severely head-injured patients could really be applied, they would probably have a considerable impact in terms of reduction in mortality and disability. Since 1995 a Group of Italian Neurointensivists and Neurosurgeons belonging to the Italian Societies of Neurosurgery (SINch) and Anesthesiology & Intensive Care (SIAARTI) has produced this first part of recommendations that are completed by Medical treatment (Part II) and Surgical treatment criteria (Part III). These recommendations reflect a multidisciplinary consent but are based on scientific evidence, when available, and take origin mainly from expert opinions and the current clinical and organizational situation. For this aspect they differ from other American and European guidelines, which are strictly based on criteria of proven efficacy. These recommendations aim at providing a practical reference for all those dealing with severe head injuries from first-aid to intensive care units, setting out the minimal goals of management to be reached throughout the country. For these reasons they need continual critical review and updating. Main clinical aims are: 1) to prevent secondary cerebral damage by continuous and meticulous maintenance of systemic homeostasis 2) to standardize methods of neurological evaluation and CT scan classification and scheduling; 3) to give simple indications for systemic and cerebral monitoring 4) to pragmatically discuss the organizational scenarios and specify the minimal safe clinical approach when patients are treated in non-specialized settings. Briefly, smooth tracheal intubation and ventilation in all comatose patients, administration of rapidly metabolized sedative and analgesic drugs to permit frequent neurological evaluation, restoration of volemia and systolic blood pressure above 110 mm Hg, oxygen saturation >95% and normocapnia, are all recommended from the very early treatment and transport. Homogeneity of language, reliable and correctly tested Glasgow Coma Score and pupillary reflexes, and a simple CT scan classification are recommended to improve communications and clinical decisions in the multidisciplinary setting of management. In comatose patients, cerebral perfusion pressure, intracranial pressure and oxygen jugular saturation must be monitored according to specific criteria, which are described. Therapy with hyperventilation and mannitol should be used only in case of clinical deterioration and uncal herniation. This therapy could be useful to gain time to reach neurosurgery. The aim of these recommendations is to achieve safer management of severely brain injured patients, immediate diagnosis of clinical deterioration and successful identification and treatment of surgical lesions. The impact of these guidelines requires further verification.

The Guidelines of the surgical management of severe head injury in adults, as evolved by the Neurotraumatology Group of the Italian Neurosurgery Society and the Italian Society for Anaesthesia, Analgesia, Reanimation and Intensive Care are presented and briefly discussed. Guidelines presented here are of a pragmatic nature, based on consensus and expert opinion. Aspects pertaining to specific indications to surgery and/or to the possibility of conservative management of different traumatic intracranial lesions are highlighted. The importance of surgery in preventing secondary insults to the traumatised brain is emphasised.