REVIEW URRENT C OPINION
Neurocritical care: why does it make a difference? Andreas H. Kramer a and David A. Zygun b
Purpose of review The care of critically ill brain-injured patients is complex and requires careful balancing of cerebral and systemic treatment priorities. A growing number of studies have reported improved outcomes when patients are admitted to dedicated neurocritical care units (NCCUs). The reasons for this observation have not been definitively clarified. Recent findings When recently published articles are combined with older literature, there have been more than 40 000 patients assessed in observational studies that compare neurological and general ICUs. Although results are heterogeneous, admission to NCCUs is associated with lower mortality and a greater chance of favorable recovery. These findings are remarkable considering that there are few interventions in neurocritical care that have been demonstrated to be efficacious in randomized trials. Whether the relationship is causal is still being elucidated but potential explanations include higher patient volume and, in turn, greater clinician experience; more emphasis on and adherence to protocols to avoid secondary brain injury; practice differences related to prognostication and withdrawal of life-sustaining interventions; and differences in the use and interpretation of neuroimaging and neuromonitoring data. Summary Neurocritical care is an evolving field that is associated with improvements in outcomes over the past decade. Further research is required to determine how monitoring and treatment protocols can be optimized. Keywords intracerebral hemorrhage, intracranial pressure, neurocritical care, subarachnoid hemorrhage, traumatic brain injury
INTRODUCTION Patients with neurological conditions account for 10–15% of all ICU admissions [1]. The care of critically ill patients with severe brain and spinal cord injuries is complex. Clinicians are often forced to balance competing concerns: interventions that are optimal for the central nervous system may be harmful for other organ systems and vice versa. Examples of neurological complications that may arise include cerebral edema, intracranial hypertension, hematoma expansion, hydrocephalus, cerebral vasospasm and nonconvulsive seizures. Systemic complications and nonneurological multiple organ dysfunction are also common and can contribute to secondary neurological injury [2,3]. At some centers, patients are admitted to multisystem medical or surgical ICUs. In this case, the most responsible physician is often a general intensivist. These clinicians and the bedside nurses they work with have particular expertise in caring for patients with multiple organ failure, but may be less experienced in recognizing and treating specific neurological complications or in the use www.co-criticalcare.com
of neurological imaging and monitoring. At other centers, patients are admitted to a dedicated neurological ICU. In this case, a neurosurgeon or neurologist may be responsible for primary medical care. These individuals, together with specialized neuroscience nurses may be particularly skilled at monitoring, detecting and treating neurological complications, but often require heavy consultative support to address systemic concerns. Over the past decade, neurocritical care has emerged as a subspecialty of critical care medicine that seeks to combine the strengths of both of these models [4]. A growing number of medical centers a Departments of Critical Care Medicine and Clinical Neurosciences, University of Calgary, Calgary and bDivision of Critical Care Medicine, University of Alberta, Edmonton, Alberta, Canada
Correspondence to Andreas H. Kramer, Clinical Associate Professor, Department of Critical Care Medicine Foothills Hospital, McCaig Tower, 3134 Hospital Drive NW Calgary, AB T2N 2T9, Canada. Tel: +1 403 944 4749; e-mail: [email protected] Curr Opin Crit Care 2014, 20:174–181 DOI:10.1097/MCC.0000000000000076 Volume 20 Number 2 April 2014
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Neurocritical care: why does it make a difference? Kramer and Zygun
KEY POINTS A large body of observational studies involving more than 40 000 patients suggests that neurological outcomes are improved when brain-injured patients are cared for in specialized NCCUs, specially when there is an involvement of neurointensivists. The key paradigm of neurocritical care is meticulous attention to the prevention and treatment of neurological and systemic factors that may contribute to secondary brain injury. Possible explanations for improved outcomes in NCCUs include higher patient volume (and, in turn, more clinician experience), greater adherence to protocols, differences in the use and interpretation of neuromonitoring data, and a more conservative approach to the withdrawal of life-sustaining interventions. Predicting the prognosis of neurocritical care patients is challenging – clinicians must strive to avoid unjustified ‘therapeutic nihilism’, while still maintaining a realistic and compassionate approach to end-of-life care.
necessarily being attributable to content expertise in neurocritical care. Two studies were methodologically stronger, in that they involved multiple centers and utilized concurrent controls; in both cases, a significant improvement in outcomes of patients with intracerebral hemorrhage (ICH) was observed when care was provided in a NCCU [10,11]. Over the past 2 years, there have been additional publications, most of which have reached similar conclusions. Damian et al. [12 ] used the Intensive Care National Audit and Research Center database to compare outcomes between general and neurological ICUs in the United Kingdom among patients with Guillain–Barre syndrome, myasthenia gravis and ICH. Even after adjusting for multiple potential confounders, mortality was lower when patients with ICH were cared for in a neurological unit. Because of its large size, multicenter design and the ability to perform robust multivariable analyses, this study provides perhaps the most compelling data to date demonstrating lower mortality in NCCUs, albeit for a selected group of patients. Pineda et al. [13 ] performed a retrospective study of 123 pediatric patients with severe traumatic brain injury (TBI) before and after the implementation of a ‘neurocritical care program’. This program consisted of an evidence-based protocol, aimed also at improving communication between different specialties, rather than involving any new personnel or equipment. The proportion of patients discharged home increased in the more recent time period, although this observation appeared to be partially attributable to a shift from inpatient to outpatient rehabilitation. Follow-up was relatively brief, and there was no difference in Glasgow Outcome Scales scores. Patients cared for in the second time block were more likely to receive intracranial pressure (ICP) monitoring and intensive therapy for intracranial hypertension. Kramer and Zygun [14 ] performed a population-based study involving more than 4000 consecutive and diverse neurocritical care patients admitted to four ICUs over more than 11 years. Mortality decreased over time and the proportion of patients discharged home without the need for support services increased. It is important to recognize that these measures do not necessarily prove improved long-term functional outcome. The effects were most pronounced among TBI and subarachnoid hemorrhage (SAH) patients. Various practice modifications were temporally associated with outcome improvements, including the hiring of neurointensivists; use of a temperature regulation protocol; mutual rounds involving the neurocritical care and neurosurgery services; implementation of a TBI protocol; and clustering of neurocritical care &&
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have dedicated neurocritical care units (NCCUs) with multidisciplinary care directed by neurointensivists. Neurointensivists are physicians from a variety of backgrounds that have acquired advanced skills in, and have devoted a large part of their clinical practice toward, the care of critically ill neurological patients. Ideally, these individuals work closely with other health professionals, including nurses, respiratory therapists, physiotherapists and social workers that also have a particular interest in the care of brain injury [5–8].
DO NEUROCRITICAL CARE UNITS IMPROVE OUTCOMES? A large body of literature suggests that outcomes are improved when care is provided in dedicated NCCUs, specially when there is an involvement of neurointensivists. A systematic review and metaanalysis published in 2011 identified 12 studies, including greater than 24 000 patients, and concluded that patients cared for in a specialty ICU were less likely to die and more likely to have a favorable neurological recovery [9]. However, there was marked heterogeneity in the methodology and results of individual studies. Most were single center comparisons with historical controls that had considerable potential for publication bias and a ‘Hawthorne effect’. Some of the observed benefit may have had more to do with a transition to a better-organized, intensivist-led team, rather than
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patients within a multidisciplinary unit. A pronounced reduction in the proportion of patients progressing to brain death over time also was observed, with the natural consequence being that there were fewer deceased organ donors [15 ]. Knopf et al. [16] reported a single-center study assessing outcomes in over 2000 stroke patients with and without the involvement of a neurointensivist. Mortality was lower and discharge disposition improved in the presence of a neurointensivist for patients with SAH, but not ICH. Loss of neurointensivist services was associated with worsened outcomes in patients with ischemic stroke. Burns et al. [17] assessed outcome in 74 ICH patients in the 12 months before and after the arrival of a neurointensivist and creation of a neurocritical care service, which functioned within a multisystem ICU. Outcomes did not change significantly, although certain ‘quality-of-care indicators’ increased, including timely implementation of nutrition and adequate control of hypertension. Improvements in outcome over time can occur even without a defined change in the model of care. Tsitsopoulos et al. [18] performed a study that compared patients with thalamic ICH in 1990–1994 versus 2005–2009. In both epochs, patients were cared for in a dedicated neurological ICU. Although baseline characteristics were similar, patients in the more recent years had a substantially lower mortality (62 versus 19%). However, a higher proportion of survivors had persistent severe disability (modified Rankin score 4–5 in 48%). Naval et al. [19] assessed outcomes in more than 1000 patients with SAH over an 18-year period at a single institution. The proportion with a Glasgow Outcome Scale score of 4 or 5 (‘favorable outcome’) increased from 65% in 1991–2000 to 72% in 2001–2009, despite more severe baseline neurological impairment in the recent group. A NCCU existed throughout the entire time period and changes in the model of care were not described. Varelas et al. [20] compared outcomes for patients with status epilepticus treated in a neurological or a medical ICU. Continuous electroencephalography was used more commonly in the neurological ICU. Outcomes did not differ, but the significance of this finding is difficult to interpret given that the characteristics of the two groups of patients were very different. We repeated the search strategy used for the previously published systematic review comparing outcomes in general and neurological ICUs, instead using the dates February 2011 to October 2013 [9]. The results of six new studies were combined with previous literature for an updated meta-analysis [12 ,13 ,14 ,16,17,20]. The combined results, now &
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including greater than 40 000 patients, confirm the previous analysis. Although there is a marked heterogeneity, the cumulative results indicate a reduction in mortality (Fig. 1; odds ratio, OR 0.72, 95% confidence interval, CI 0.59–0.89, P ¼ 0.002; I2 ¼ 91%) and poor neurological recovery (Fig. 2; OR 0.70, 95% CI 0.61–0.81, P < 0.0001; I2 ¼ 76%) when patients with acute brain injury are cared for in a neurological ICU. There are also studies showing that delays in transferring patients from emergency departments to NCCUs may have adverse consequences. Rincon et al. [21] reported that in stroke patients, an emergency department length of stay greater than 5 h before transfer to a NCCU was predictive of poor outcomes. At least three studies also have found that outcomes are worse when patients are transferred to the NCCU from another institution rather than the local emergency department, possibly because of delays in care [22–24]. Although these studies do not compare neurological and general ICUs, the results emphasize the need for urgent attention by specialists. Together the data are compelling and suggest that the presence of neurocritical care is associated with better outcomes in patients with acute neurological disease. However, exactly what constitutes ‘neurocritical care’, for example a dedicated unit, organization of protocols or a neurointensivist in a general ICU, whether the effect applies to all neurologic diseases and whether the effect is causal still require clarification. Existing studies also are not entirely clear concerning the specific factors that contribute to improved outcomes in NCCUs. However, a review of published data makes it possible to generate reasonable hypotheses.
EFFECT OF PATIENT VOLUME There are many studies, involving a variety of diagnoses, which suggest a relationship between the volume of patients cared for in an institution and more favorable outcomes. These observations were made initially for major surgical procedures, but also are reported for various medical disorders, including conditions common to ICUs [25–29]. Higher hospital volume has been associated with improved outcomes in patients with ischemic stroke, ICH, SAH and TBI [30–34], as well as for common neurosurgical procedures [35,36]. In the study by Damian et al. [12 ], the annual rate of ICU admissions for ICH in the United Kingdom was more than seven-fold to eight-fold greater in NCCUs than in general ICUs (mean of 34 admissions versus 4–5 per year). Given that there are usually several intensivists who work in a general &&
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Neurocritical care: why does it make a difference? Kramer and Zygun
Outcome
Yes/Total NCC
Odds ratio and 95% CI
No NCC
p-Value
Warme
Mortality
23/72
20/49
0.318
Diringer
Mortality
93/266
310/771
0.131
Mirski
Mortality
15/78
18/50
0.037
Elf
Mortality
9/154
22/72
0.000
Patel
Mortality
41/202
19/83
0.626
Suarez
Mortality
97/1180
127/1201
0.050
Varelas
Mortality
116/1279
110/1087
0.387
Lerch
Mortality
5/36
5/23
0.436
Lott (ICH)
Mortality
1199/5993
1461/5875
0.000
Lott (IS)
Mortality
314/1446
661/3101
0.760
Palminteri
Mortality
36/164
30/123
0.627
Josephson
Mortality
54/296
29/216
0.145
Samuels
Mortality
98/386
85/317
0.668
Knopf
Mortality
405/1372
278/724
0.000
Kramer
Mortality
884/2627
4337/1470
0.005
Damian (ICH)
Mortality
1694/3753
4337/6560
0.000
Pineda
Mortality
2/60
7/63
0.118
Varelas (SE)
Mortality
2/46
10/122
0.396
Burns
Mortality
3/37
1/37
0.327
5090/19447
8089/21944
0.002 0.1
0.2
0.5
Favors NCC
1
2
5
10
Favors control
Meta analysis
FIGURE 1. Observational studies comparing mortality between specialty neurological ICUs and alternative models of care.
ICU, it is likely that, on average, they were caring for only one to two ICH patients per year, making it difficult to establish expertise. In the study by Diringer and Edwards [10], patients with ICH that were admitted to a NCCU were also all cared for at the largest hospitals, all of which were affiliated with medical schools. A larger number of ICU beds and ICH admissions were found to be independent predictors of lower mortality. Similarly, in the study by Lott et al. [11], 50% of all patients were admitted to a NCCU, even though only 18% of hospitals had such units. These findings suggest that experience matters in the quality of care provided to neurocritical care patients. There continue to be unanswered questions about the effects of patient volume. For example, is it institutional or individual clinician volume that is more important? Are there thresholds that define adequate volume? What effects, if any, do residency work hour restrictions have? This may be important even for common neurosurgical conditions. A recent analysis of the Nationwide Inpatient Sample assessed more than 20 000 patients who had elective meningioma resections and found that postoperative complications were increased at teaching hospitals, but not at
nonteaching hospitals after the introduction of work hour restrictions [37].
ADHERENCE TO PROTOCOLS Very few specific interventions that are commonly used in the NCCU have been demonstrated to improve outcomes in large randomized trials. Most treatments recommended by international guidelines are based on relatively low-quality evidence that is derived primarily from observational studies or based on physiological principles [38–41]. For example, it is common practice to avoid hypotension or derangements in the partial pressure of oxygen or carbon dioxide [42,43]. Even mild abnormalities in core body temperature and serum glucose or sodium concentration are treated expeditiously [44–46]. Electroencephalography is used liberally to detect and treat nonconvulsive seizures [47]. Although it may be difficult to prove that any one of these interventions makes a difference on its own, it is possible that in combination they have a powerful effect. Avoidance of ‘secondary’ neurological insults is the underlying principle used in neurocritical care protocols, which essentially function as a checklist for ‘best practice’.
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Study name
Outcome
Yes/Total
Odds ratio and 95% CI
NCC
No NCC
p-Value
Warme
Poor outcome
37/72
33/49
0.083
Mirski
Poor outcome
24/78
26/50
0.017
Elf
Poor outcome
34/154
38/72
0.000
Patel
Poor outcome
68/202
37/83
0.084
Suarez
Poor outcome
512/1180
551/1201
0.222
Varelas
Poor outcome
516/1279
525/1087
0.000
Lerch
Poor outcome
13/39
13/23
0.127
Lott (ICH)
Poor outcome
3110/5993
3459/5875
0.000
Lott (IS)
Poor outcome
908/1446
1968/3101
0.663
Palminteri
Poor outcome
62/164
48/123
0.833
Samuels
Poor outcome
245/386
237/317
0.001
Knopf
Poor outcome
722/1372
493/724
0.000
Kramer
Poor outcome
1444/2390
730/1107
0.002
Pineda
Poor outcome
20/60
33/63
0.034
Varelas (SE)
Poor outcome
36/46
94/122
0.867
Burns
Poor outcome
30/37
24/37
0.121
7781/14985
8309/14034
0.000
0.1
0.2
0.5
Favors NCC
1
2
5
10
Favors control
Meta analysis
FIGURE 2. Observational studies comparing the proportion of patients developing poor outcomes between specialty neurological ICUs and alternative models of care.
In several studies that observed improved outcomes with neurocritical care, the primary ‘intervention’ was a comprehensive protocol [13 ,48,49]. A recent systematic review assessed studies comparing the use of ‘management protocols’ with ‘standard’ care among patients with TBI and reported that the use of protocols was associated with reduced mortality and more favorable neurological recovery [50 ]. Compliance with Brain Trauma Foundation guidelines has also been linked with improved outcomes in some studies [51–53]. &
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LENGTH OF STAY AND WITHDRAWAL OF LIFE-SUSTAINING INTERVENTIONS Although some single-center studies suggest the opposite [54,55], much of the data indicate that ICU length of stay is longer and resource use more intensive when patients are cared for in a NCCU [10,12 ,13 ,16,17,56]. Damian et al. [12 ] found that adjustment for length of stay modified the impact of the type of ICU on hospital mortality. In a population-based study showing improved outcomes over time, length of ICU stay also increased &&
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significantly [14 ]. It is possible that longer length of stay is a marker of a more aggressive approach to patient care [56], or a more cautious disposition toward withdrawal of life-sustaining interventions. Only a small and declining proportion of NCCU patients progress to brain death [15 ]. Unanticipated cardiac arrests after admission to the ICU are rare. In most cases of mortality, death occurs after withdrawal of life-sustaining interventions, primarily mechanical ventilation, based on the perception that the prognosis for a favorable neurological recovery is poor [57–59]. Physicians usually initiate conversations about limitations in care [60]. If the best possible functional or cognitive outcome is one that would not be acceptable to a patient, then withdrawal of life-sustaining interventions may be entirely appropriate and necessary [61]. However, accurate outcome prediction is difficult [62]. Clinicians’ perceptions about prognosis, and in turn their recommendations to patients’ families, may be heterogeneous and influenced by factors other than just patient preferences or the severity of brain injury. Physician experience may be one such factor [63,64 ]. In a Canadian survey about the prognosis &
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of TBI patients, neurologists (who were the least likely to be involved in the care of such patients) were considerably more pessimistic than intensivists or neurosurgeons [64 ]. Another study using a clinical vignette involving a patient with anoxic brain injury reported that recommendations on life-support withdrawal were influenced by physician age and experience, years in practice, and whether or not they provided long-term follow-up for patients [65]. Some studies suggest that physicians are generally more pessimistic than is justified by existing information [66,67]. Unfortunately, available tools to aid in the prediction of long-term prognosis are imperfect [68]. Recent data demonstrate that there is significant variability in the frequency and timing of withdrawal of life-sustaining therapies between institutions [69]. One multicenter study observed that tracheostomies are more likely in NCCUs, which may suggest a greater reluctance toward treatment withdrawal [56]. The best evidence for improved outcomes in NCCUs comes from studies of ICH patients [10,11,12 ], in which the concept of treatment withdrawal leading to ‘self-fulfilling prophecy’ has been best described [66,70–72]. Nevertheless, despite these observations, it remains unclear whether there are systematic differences in withdrawal of life-support practices based on the type of ICU where patients receive their care. &
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MULTIMODAL NEUROLOGICAL MONITORING In studies that compare outcomes of TBI patients in neurological and general ICUs, the use of ICP monitoring was one of several interventions that were more common in neurological units [48,49,69]. In general, increased use of ICP monitoring, used with a detailed management protocol, has been associated with more favorable outcomes in observational studies, although results are somewhat variable [50 ,73]. The Benchmark Evidence from South American Trials : Treatment of Intracranial Pressure study was a randomized trial performed in general ICUs in South America that compared two management protocols, one with and the other without ICP monitoring. There was a trend toward lower early mortality with ICP monitors, but 6-month outcomes were similar [74]. There were several study limitations, which have been discussed at length in the study correspondence and subsequent editorials. Importantly, ICP monitoring differed from the way it is used in many NCCUs, so limiting the study’s external validity. For example, monitoring was provided for a median of only 3.6 days (interquartile range &
2.0–6.6 days), even though intracranial hypertension frequently persists longer than this [75,76]. Patients without monitors received more osmotic therapy and hyperventilation, whereas the pressuremonitored group received more barbiturates, a therapy that is now infrequently used at many centers. Furthermore, cerebrospinal fluid drainage was almost never used and almost one-third of the nonmonitored patients underwent early decompressive craniectomy, which in turn may have attenuated any benefit from ICP monitoring. Neurocritical care patients are heterogeneous. Even within a particular diagnostic subgroup like TBI, it seems unlikely that targeting a single treatment threshold in all patients (e.g. ICP < 20 mmHg) represents the optimal approach. Increasingly, neurointensivists integrate ICP and cerebral perfusion pressure with other information, including neuroimaging, intracranial compliance, cerebral blood flow autoregulation and information derived from other modes of neurological monitoring before making treatment decisions [77–80]. Indeed, the theoretical advantage of multimodal monitoring is individualization of therapeutic targets based on the specific characteristics of a patient. Existing publications assessing multimodal monitoring, for example with use of both ICP and brain tissue oxygen monitors, have reached conflicting conclusions, with some studies suggesting benefit and others indicating either no effect or even harm [81–85]. The efficacy of brain tissue oxygen monitoring is currently being assessed in the Brain Tissue Oxygen Monitoring in Traumatic Brain Injury (BOOST 2) trial [86]. It seems obvious that the usefulness of any monitoring device depends on what clinicians do with the acquired information. A potential advantage of multimodal monitoring may be that it promotes awareness of the cerebral effects of common day-to-day interventions in the ICU. For example, using multimodal monitoring, researchers have reported deleterious effects attributable to sedation interruption [87,88], fiberoptic bronchoscopy [89], percutaneous tracheostomy insertion [90], and patient transport for diagnostic procedures [91]. Intensivists may perform or facilitate these interventions without any knowledge of the cerebral implications. NCCUs usually have a ‘culture’ that strongly emphasizes neuroprotection, with careful consideration of the cerebral effects of any intervention.
CONCLUSION In summary, a large body of evidence demonstrates that outcomes are improved when braininjured patients are cared for in NCCUs. A variety
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of organizational models have been used to effectively deliver such care. Future studies should seek to better understand which specific practices are most important and whether or how the observed relationship is causal. Much research is required to clarify how management protocols can be optimized to further reduce mortality and maximize neurological recovery. Acknowledgements None. Conflicts of interest This manuscript has not been published previously. It has not been submitted to another journal. The authors have no conflicts of interest to declare.
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Temporal trends and volume-outcome associations after traumatic brain injury: a 12-year study in Taiwan. J Neurosurg 2013; 118:732–738. 35. Barker FG 2nd, Amin-Hanjani S, Butler WE, et al. In-hospital mortality and morbidity after surgical treatment of unruptured intracranial aneurysms in the United States, 1996–2000; the effect of hospital and surgeon volume. Neurosurgery 2003; 52:995–1007. 36. Hoh BL, Rabinov JD, Pryor JC, et al. In-hospital morbidity and mortality after endovascular treatment of unruptured intracranial aneurysms in the United States, 1996–2000: effect of hospital and physician volume. Am J Neuroradiol 2003; 24:1409–1420. 37. Dumont TM, Tranmer BI, Horgan MA, Rughani AI. Trends in neurosurgical complication rates at teaching vs nonteaching hospitals following duty-hour restrictions. Neurosurgery 2012; 71:1041–1046. 38. Diringer MN, Bleck TP, Hemphill JC, et al. Critical care management of patients following aneurysmal subarachnoid hemorrhage: recommendations from the Neurocritical Care Society’s Multidisciplinary Consensus Conference. Neurocrit Care 2011; 15:211–240. 39. Brain Trauma Foundation, American Association of Neurological Surgeons, Congress of Neurological Surgeons. Guidelines for the management of severe traumatic brain injury. J Neurotrauma 2007; 24:S1–S106. 40. Brophy GM, Bell R, Claassen J, et al. Guidelines for the evaluation and management of status epilepticus. Neurocrit Care 2012; 17:3–23.
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Neurocritical care: why does it make a difference? Kramer and Zygun 41. Morgenstern LB, Hemphill JC, Anderson C, et al. Guidelines for the management of spontaneous intracerebral hemorrhage: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2010; 41:2108–2129. 42. Davis DP, Meade W, Sise MJ, et al. Both hypoxemia and extreme hyperoxemia may be detrimental in patients with severe traumatic brain injury. J Neurotrauma 2009; 26:2217–2223. 43. Davis DP, Idris AH, Sise MJ, et al. Early ventilation and outcome in patients with moderate to severe traumatic brain injury. Crit Care Med 2006; 34: 1202–1208. 44. Badjatia N. Hyperthermia and fever control in brain injury. Crit Care Med 2009; 37:S250–S257. 45. Kramer AH, Roberts DJ, Zygun DA. Optimal glycemic control in neurocritical care patients: a systematic review and meta-analysis. Crit Care 2012; 22:R203. 46. Wright WL. Sodium and fluid management in acute brain injury. Curr Neurol Neurosci Rep 2012; 12:466–473. 47. Kramer AH, Jette N, Pillay N, et al. Epileptiform activity in neurocritical care patients. Can J Neurol Sci 2012; 39:328–337. 48. Elf K, Nilsson P, Enblad P. Outcome after traumatic brain injury improved by an organized secondary insult program and standardized neurointensive care. Crit Care Med 2002; 30:2129–2134. 49. Patel HC, Menon DK, Tebbs S, et al. Specialist neurocritical care and outcome from head injury. Intensive Care Med 2002; 28:547–553. 50. English SW, Turgeon AF, Owen E, et al. Protocol management of severe & traumatic brain injury in intensive care units: a systematic review. Neurocrit Care 2013; 18:131–142. This systematic review identified 13 observational studies that compared outcomes in patients with and without a ‘protocol’. In most cases, the outcomes were compared with historical controls from the same institution and the ‘protocol’ group had a defined algorithm for the management of ICP and CPP. The rate of favorable outcomes at 6 months strongly favored the intervention group (OR 3.84, 95% CI 2.47–5.96). 51. Fakhry SM, Trask AL, Waller MA, Watts DD. Management of brain-injured patients by an evidence-based medicine protocol improves outcomes and decreases hospital charges. J Trauma 2004; 56:492–499. 52. Talving P, Karamanos E, Teixeira PG, et al. Intracranial pressure monitoring in severe head injury: compliance with Brain Trauma Foundation guidelines and effect on outcomes. J Neurosurg 2013; 119:1248–1254. 53. Palmer S, Bader MK, Qureshi A, et al. The impact on outcomes in a community hospital setting using the AANS traumatic brain injury guidelines. J Trauma 2001; 50:657–754. 54. Mirski MA, Chang CWJ, Cowan R. Impact of a neuroscience intensive care unit on neurosurgical patient outcomes and cost of care. J Neurosurg Anesthesiol 2001; 13:83–92. 55. Suarez JI, Zaidat OO, Suri MF, et al. Length of stay and mortality in neurocritically ill patients: impact of a specialized neurocritical care team. Crit Care Med 2004; 32:2311–2317. 56. Kurtz P, Fitts V, Sumer Z, et al. How does care differ for neurological patients admitted to a neurocritical care unit versus a general ICU? Neurocrit Care 2011; 15:477–480. 57. Sise MJ, Sise CB, Thorndike JF, et al. Withdrawal of care: a 10-year perspective at a Level I trauma center. J Trauma Acute Care Surg 2012; 72:1186–1193. 58. Holloway RG, Quill TE. Treatment decisions after brain injury: tensions among quality, preference, and cost. N Engl J Med 2010; 362:1757–1820. 59. Verkade MA, Epker JL, Nieuwenhoff MD, et al. Withdrawal of life-sustaining treatment in a mixed intensive care unit: most common in patients with catastrophic brain injury. Neurocrit Care 2012; 16:130–135. 60. Estaban A, Gordo F, Soisona JF, et al. Withdrawing and withholding life support in the intensive care unit: a Spanish prospective multicentre observational study. Intensive Care Med 2001; 27:1744–1749. 61. Smith M. Treatment withdrawal and acute brain injury: an integral part of care. Anaesthesia 2012; 67:941–945. 62. Finley Caulfield A, Gabler L, Lansberg MG, et al. Outcome prediction in mechanically ventilated neurologic patients by junior neurointensivists. Neurology 2010; 74:1096–1101. 63. Cook DJ, Guyatt GH, Jaeschke R, et al. Determinants in Canadian healthcare workers of the decision to withdraw life support from the critically ill. JAMA 1995; 273:703–708. 64. Turgeon AF, Lauzier F, Burns KE, et al. Determination of neurologic prognosis & and clinical decision making in adult patients with severe traumatic brain injury: a survey of Canadian intensivists, neurosurgeons, and neurologists. Crit Care Med 2013; 41:1086–1093. This survey had a well defined sampling frame and a relatively high response rate of more than 60%. Significant variability was observed in clinicians’ perception of the prognosis of a young TBI patient with a Glasgow Coma Scale score of 6 and in clinicians’ approach to withdrawal of life-sustaining interventions.
65. Racine E, Dion MJ, Wijman CA, et al. Profiles of neurological outcome prediction among intensivists. Neurocrit Care 2009; 11:345–362. 66. Rocker GM, Cook DJ, Shemie SD. Brief review: practice variation in end of life care in the ICU: implications for patients with severe brain injury. Can J Anesth 2006; 53:814–819. 67. Becker KJ, Baxter AB, Cohen WA, et al. Withdrawal of support in intracerebral hemorrhage may lead to self-fulfilling prophecies. Neurology 2001; 56:766– 772. 68. Stevens RD, Sutter R. Prognosis in severe brain injury. Crit Care Med 2013; 41:1104–1123. 69. Turgeon AF, Lauzier F, Simard JF, et al. Mortality associated with withdrawal of life-sustaining therapy for patients with severe traumatic brain injury: a Canadian multicenter cohort study. CMAJ 2011; 183:1581. 70. Creutzfeld CJ, Becker KJ, Weinstein JR, et al. Do-not-attempt-resuscitation orders and prognostic models for intraparenchymal hemorrhage. Crit Care Med 2011; 39:158–162. 71. Zahuranec DB, Brown DL, Lisabeth LD, et al. Early care limitations independently predict mortality after intracerebral hemorrhage. Neurology 2007; 68:1651–1657. 72. Hemphill JC, Newman J, Zhao S, Johnston SC. Hospital usage of early do-notresuscitate orders and outcome after intracerebral hemorrhage. Stroke 2004; 35:1130–1134. 73. Cremer OL, Van Dijk GW, Van Wensen E, et al. Effect of intracranial pressure monitoring and targeted intensive care on functional outcome after severe head injury. Crit Care Med 2005; 33:2207–2213. 74. Chesnut RM, Temkin N, Carney N, et al. A trial of intracranial-pressure monitoring in traumatic brain injury. N Engl J Med 2012; 367:2471– 2481. 75. Stein DM, Brenner M, Hu PF, et al. Timing of intracranial hypertension following severe traumatic brain injury. Neurocrit Care 2013; 18:332– 340. 76. O’Phelan KH, Park D, Efird JT, et al. Patterns of increased intracranial pressure after severe traumatic brain injury. Neurocrit Care 2009; 10:280–286. 77. Lazararidis C, DeSantis SM, Smielewski P, et al. Patient-specific thresholds of intracranial pressure in patients with severe traumatic brain injury. Neurocrit Care 2013; 19:S21. 78. Aries MJ, Czosnyka M, Budohoski KP, et al. Continuous determination of optimal cerebral perfusion pressure in traumatic brain injury. Crit Care Med 2012; 40:2456–2463. 79. Howells T, Lewen A, Skold MK, et al. An evaluation of three measures of intracranial compliance in traumatic brain injury patients. Intesnive Care Med 2012; 38:1061–1068. 80. Stocchetti N, LeRoux PL, Vespa P, et al. Clinical review: neuromonitoring: an update. Crit Care 2013; 17:201. 81. Green JA, Pelligrini DC, Vanderkolk WE, et al. Goal directed brain tissue oxygen monitoring versus conventional management in traumatic brain injury: an analysis of in hospital recovery. Neurocrit Care 2013; 18:20–25. 82. Spiotta AM, Stiefel MF, Gracias VH, et al. Brain tissue oxygen-directed management and outcome in patients with severe traumatic brain injury. J Neurosurg 2010; 113:571–580. 83. Martini RP, Deem S, Yanez ND, et al. Management guided by brain tissue oxygen monitoring and outcome following severe traumatic brain injury. J Neurosurg 2009; 111:644–649. 84. Stiefel MF, Spiotta A, Graias VH, et al. Reduced mortality rate in patients with severe traumatic brain injury treated with brain tissue oxygen monitoring. J Neurosurg 2005; 103:805–811. 85. Nangunoori R, Maloney-Wilensy E, Stiefel M, et al. Brain tissue oxygen-based therapy and outcome after severe traumatic brain injury: a systematic literature review. Neurocrit Care 2012; 17:131–138. 86. http://www.clinicaltrials.gov/ct2/show/NCT00974259?term¼boostþandþ andþ tbi&rank¼1. [Accessed 1 August 2013] 87. Helbok R, Kurtz P, Schmidt MJ, et al. Effects of the neurological wake-up test on clinical examination, intracranial pressure, brain metabolism and brain tissue oxygenation in severely brain-injured patients. Crit Care 2012; 16: R226. 88. Skoglund K, Hillered L, Purins K, et al. The neurological wake-up test does not alter cerebral energy metabolism and oxygenation in patients with severe traumatic brain injury. Neurocrit Care 2013. [Epub ahead of print] 89. Kerwin AJ, Croce MA, Timmons SD, et al. Effects of fiberoptic bronchoscopy on intracranial pressure in patients with brain injury: a prospective clinical study. J Trauma 2000; 48:878–882. 90. Kleffman J, Pahl R, Deinsberger W, et al. Effect of percutaneous tracheostomy on intracerebral pressure and perfusion pressure in patients with acute cerebral dysfunction (TIP Trial): an observational study. Neurocrit Care 2012; 17:85–89. 91. Swanson EW, Mascitelli J, Stiefel M, et al. Patient transport and brain oxygen in comatose patients. Neurosurgery 2010; 66:925–931.
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Neurocritical care: why does it make a difference? Andreas H. Kramer a and David A. Zygun b
Purpose of review The care of critically ill brain-injured patients is complex and requires careful balancing of cerebral and systemic treatment priorities. A growing number of studies have reported improved outcomes when patients are admitted to dedicated neurocritical care units (NCCUs). The reasons for this observation have not been definitively clarified. Recent findings When recently published articles are combined with older literature, there have been more than 40 000 patients assessed in observational studies that compare neurological and general ICUs. Although results are heterogeneous, admission to NCCUs is associated with lower mortality and a greater chance of favorable recovery. These findings are remarkable considering that there are few interventions in neurocritical care that have been demonstrated to be efficacious in randomized trials. Whether the relationship is causal is still being elucidated but potential explanations include higher patient volume and, in turn, greater clinician experience; more emphasis on and adherence to protocols to avoid secondary brain injury; practice differences related to prognostication and withdrawal of life-sustaining interventions; and differences in the use and interpretation of neuroimaging and neuromonitoring data. Summary Neurocritical care is an evolving field that is associated with improvements in outcomes over the past decade. Further research is required to determine how monitoring and treatment protocols can be optimized. Keywords intracerebral hemorrhage, intracranial pressure, neurocritical care, subarachnoid hemorrhage, traumatic brain injury
INTRODUCTION Patients with neurological conditions account for 10–15% of all ICU admissions [1]. The care of critically ill patients with severe brain and spinal cord injuries is complex. Clinicians are often forced to balance competing concerns: interventions that are optimal for the central nervous system may be harmful for other organ systems and vice versa. Examples of neurological complications that may arise include cerebral edema, intracranial hypertension, hematoma expansion, hydrocephalus, cerebral vasospasm and nonconvulsive seizures. Systemic complications and nonneurological multiple organ dysfunction are also common and can contribute to secondary neurological injury [2,3]. At some centers, patients are admitted to multisystem medical or surgical ICUs. In this case, the most responsible physician is often a general intensivist. These clinicians and the bedside nurses they work with have particular expertise in caring for patients with multiple organ failure, but may be less experienced in recognizing and treating specific neurological complications or in the use www.co-criticalcare.com
of neurological imaging and monitoring. At other centers, patients are admitted to a dedicated neurological ICU. In this case, a neurosurgeon or neurologist may be responsible for primary medical care. These individuals, together with specialized neuroscience nurses may be particularly skilled at monitoring, detecting and treating neurological complications, but often require heavy consultative support to address systemic concerns. Over the past decade, neurocritical care has emerged as a subspecialty of critical care medicine that seeks to combine the strengths of both of these models [4]. A growing number of medical centers a Departments of Critical Care Medicine and Clinical Neurosciences, University of Calgary, Calgary and bDivision of Critical Care Medicine, University of Alberta, Edmonton, Alberta, Canada
Correspondence to Andreas H. Kramer, Clinical Associate Professor, Department of Critical Care Medicine Foothills Hospital, McCaig Tower, 3134 Hospital Drive NW Calgary, AB T2N 2T9, Canada. Tel: +1 403 944 4749; e-mail: [email protected] Curr Opin Crit Care 2014, 20:174–181 DOI:10.1097/MCC.0000000000000076 Volume 20 Number 2 April 2014
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Neurocritical care: why does it make a difference? Kramer and Zygun
KEY POINTS A large body of observational studies involving more than 40 000 patients suggests that neurological outcomes are improved when brain-injured patients are cared for in specialized NCCUs, specially when there is an involvement of neurointensivists. The key paradigm of neurocritical care is meticulous attention to the prevention and treatment of neurological and systemic factors that may contribute to secondary brain injury. Possible explanations for improved outcomes in NCCUs include higher patient volume (and, in turn, more clinician experience), greater adherence to protocols, differences in the use and interpretation of neuromonitoring data, and a more conservative approach to the withdrawal of life-sustaining interventions. Predicting the prognosis of neurocritical care patients is challenging – clinicians must strive to avoid unjustified ‘therapeutic nihilism’, while still maintaining a realistic and compassionate approach to end-of-life care.
necessarily being attributable to content expertise in neurocritical care. Two studies were methodologically stronger, in that they involved multiple centers and utilized concurrent controls; in both cases, a significant improvement in outcomes of patients with intracerebral hemorrhage (ICH) was observed when care was provided in a NCCU [10,11]. Over the past 2 years, there have been additional publications, most of which have reached similar conclusions. Damian et al. [12 ] used the Intensive Care National Audit and Research Center database to compare outcomes between general and neurological ICUs in the United Kingdom among patients with Guillain–Barre syndrome, myasthenia gravis and ICH. Even after adjusting for multiple potential confounders, mortality was lower when patients with ICH were cared for in a neurological unit. Because of its large size, multicenter design and the ability to perform robust multivariable analyses, this study provides perhaps the most compelling data to date demonstrating lower mortality in NCCUs, albeit for a selected group of patients. Pineda et al. [13 ] performed a retrospective study of 123 pediatric patients with severe traumatic brain injury (TBI) before and after the implementation of a ‘neurocritical care program’. This program consisted of an evidence-based protocol, aimed also at improving communication between different specialties, rather than involving any new personnel or equipment. The proportion of patients discharged home increased in the more recent time period, although this observation appeared to be partially attributable to a shift from inpatient to outpatient rehabilitation. Follow-up was relatively brief, and there was no difference in Glasgow Outcome Scales scores. Patients cared for in the second time block were more likely to receive intracranial pressure (ICP) monitoring and intensive therapy for intracranial hypertension. Kramer and Zygun [14 ] performed a population-based study involving more than 4000 consecutive and diverse neurocritical care patients admitted to four ICUs over more than 11 years. Mortality decreased over time and the proportion of patients discharged home without the need for support services increased. It is important to recognize that these measures do not necessarily prove improved long-term functional outcome. The effects were most pronounced among TBI and subarachnoid hemorrhage (SAH) patients. Various practice modifications were temporally associated with outcome improvements, including the hiring of neurointensivists; use of a temperature regulation protocol; mutual rounds involving the neurocritical care and neurosurgery services; implementation of a TBI protocol; and clustering of neurocritical care &&
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have dedicated neurocritical care units (NCCUs) with multidisciplinary care directed by neurointensivists. Neurointensivists are physicians from a variety of backgrounds that have acquired advanced skills in, and have devoted a large part of their clinical practice toward, the care of critically ill neurological patients. Ideally, these individuals work closely with other health professionals, including nurses, respiratory therapists, physiotherapists and social workers that also have a particular interest in the care of brain injury [5–8].
DO NEUROCRITICAL CARE UNITS IMPROVE OUTCOMES? A large body of literature suggests that outcomes are improved when care is provided in dedicated NCCUs, specially when there is an involvement of neurointensivists. A systematic review and metaanalysis published in 2011 identified 12 studies, including greater than 24 000 patients, and concluded that patients cared for in a specialty ICU were less likely to die and more likely to have a favorable neurological recovery [9]. However, there was marked heterogeneity in the methodology and results of individual studies. Most were single center comparisons with historical controls that had considerable potential for publication bias and a ‘Hawthorne effect’. Some of the observed benefit may have had more to do with a transition to a better-organized, intensivist-led team, rather than
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Neuroscience
patients within a multidisciplinary unit. A pronounced reduction in the proportion of patients progressing to brain death over time also was observed, with the natural consequence being that there were fewer deceased organ donors [15 ]. Knopf et al. [16] reported a single-center study assessing outcomes in over 2000 stroke patients with and without the involvement of a neurointensivist. Mortality was lower and discharge disposition improved in the presence of a neurointensivist for patients with SAH, but not ICH. Loss of neurointensivist services was associated with worsened outcomes in patients with ischemic stroke. Burns et al. [17] assessed outcome in 74 ICH patients in the 12 months before and after the arrival of a neurointensivist and creation of a neurocritical care service, which functioned within a multisystem ICU. Outcomes did not change significantly, although certain ‘quality-of-care indicators’ increased, including timely implementation of nutrition and adequate control of hypertension. Improvements in outcome over time can occur even without a defined change in the model of care. Tsitsopoulos et al. [18] performed a study that compared patients with thalamic ICH in 1990–1994 versus 2005–2009. In both epochs, patients were cared for in a dedicated neurological ICU. Although baseline characteristics were similar, patients in the more recent years had a substantially lower mortality (62 versus 19%). However, a higher proportion of survivors had persistent severe disability (modified Rankin score 4–5 in 48%). Naval et al. [19] assessed outcomes in more than 1000 patients with SAH over an 18-year period at a single institution. The proportion with a Glasgow Outcome Scale score of 4 or 5 (‘favorable outcome’) increased from 65% in 1991–2000 to 72% in 2001–2009, despite more severe baseline neurological impairment in the recent group. A NCCU existed throughout the entire time period and changes in the model of care were not described. Varelas et al. [20] compared outcomes for patients with status epilepticus treated in a neurological or a medical ICU. Continuous electroencephalography was used more commonly in the neurological ICU. Outcomes did not differ, but the significance of this finding is difficult to interpret given that the characteristics of the two groups of patients were very different. We repeated the search strategy used for the previously published systematic review comparing outcomes in general and neurological ICUs, instead using the dates February 2011 to October 2013 [9]. The results of six new studies were combined with previous literature for an updated meta-analysis [12 ,13 ,14 ,16,17,20]. The combined results, now &
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including greater than 40 000 patients, confirm the previous analysis. Although there is a marked heterogeneity, the cumulative results indicate a reduction in mortality (Fig. 1; odds ratio, OR 0.72, 95% confidence interval, CI 0.59–0.89, P ¼ 0.002; I2 ¼ 91%) and poor neurological recovery (Fig. 2; OR 0.70, 95% CI 0.61–0.81, P < 0.0001; I2 ¼ 76%) when patients with acute brain injury are cared for in a neurological ICU. There are also studies showing that delays in transferring patients from emergency departments to NCCUs may have adverse consequences. Rincon et al. [21] reported that in stroke patients, an emergency department length of stay greater than 5 h before transfer to a NCCU was predictive of poor outcomes. At least three studies also have found that outcomes are worse when patients are transferred to the NCCU from another institution rather than the local emergency department, possibly because of delays in care [22–24]. Although these studies do not compare neurological and general ICUs, the results emphasize the need for urgent attention by specialists. Together the data are compelling and suggest that the presence of neurocritical care is associated with better outcomes in patients with acute neurological disease. However, exactly what constitutes ‘neurocritical care’, for example a dedicated unit, organization of protocols or a neurointensivist in a general ICU, whether the effect applies to all neurologic diseases and whether the effect is causal still require clarification. Existing studies also are not entirely clear concerning the specific factors that contribute to improved outcomes in NCCUs. However, a review of published data makes it possible to generate reasonable hypotheses.
EFFECT OF PATIENT VOLUME There are many studies, involving a variety of diagnoses, which suggest a relationship between the volume of patients cared for in an institution and more favorable outcomes. These observations were made initially for major surgical procedures, but also are reported for various medical disorders, including conditions common to ICUs [25–29]. Higher hospital volume has been associated with improved outcomes in patients with ischemic stroke, ICH, SAH and TBI [30–34], as well as for common neurosurgical procedures [35,36]. In the study by Damian et al. [12 ], the annual rate of ICU admissions for ICH in the United Kingdom was more than seven-fold to eight-fold greater in NCCUs than in general ICUs (mean of 34 admissions versus 4–5 per year). Given that there are usually several intensivists who work in a general &&
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Neurocritical care: why does it make a difference? Kramer and Zygun
Outcome
Yes/Total NCC
Odds ratio and 95% CI
No NCC
p-Value
Warme
Mortality
23/72
20/49
0.318
Diringer
Mortality
93/266
310/771
0.131
Mirski
Mortality
15/78
18/50
0.037
Elf
Mortality
9/154
22/72
0.000
Patel
Mortality
41/202
19/83
0.626
Suarez
Mortality
97/1180
127/1201
0.050
Varelas
Mortality
116/1279
110/1087
0.387
Lerch
Mortality
5/36
5/23
0.436
Lott (ICH)
Mortality
1199/5993
1461/5875
0.000
Lott (IS)
Mortality
314/1446
661/3101
0.760
Palminteri
Mortality
36/164
30/123
0.627
Josephson
Mortality
54/296
29/216
0.145
Samuels
Mortality
98/386
85/317
0.668
Knopf
Mortality
405/1372
278/724
0.000
Kramer
Mortality
884/2627
4337/1470
0.005
Damian (ICH)
Mortality
1694/3753
4337/6560
0.000
Pineda
Mortality
2/60
7/63
0.118
Varelas (SE)
Mortality
2/46
10/122
0.396
Burns
Mortality
3/37
1/37
0.327
5090/19447
8089/21944
0.002 0.1
0.2
0.5
Favors NCC
1
2
5
10
Favors control
Meta analysis
FIGURE 1. Observational studies comparing mortality between specialty neurological ICUs and alternative models of care.
ICU, it is likely that, on average, they were caring for only one to two ICH patients per year, making it difficult to establish expertise. In the study by Diringer and Edwards [10], patients with ICH that were admitted to a NCCU were also all cared for at the largest hospitals, all of which were affiliated with medical schools. A larger number of ICU beds and ICH admissions were found to be independent predictors of lower mortality. Similarly, in the study by Lott et al. [11], 50% of all patients were admitted to a NCCU, even though only 18% of hospitals had such units. These findings suggest that experience matters in the quality of care provided to neurocritical care patients. There continue to be unanswered questions about the effects of patient volume. For example, is it institutional or individual clinician volume that is more important? Are there thresholds that define adequate volume? What effects, if any, do residency work hour restrictions have? This may be important even for common neurosurgical conditions. A recent analysis of the Nationwide Inpatient Sample assessed more than 20 000 patients who had elective meningioma resections and found that postoperative complications were increased at teaching hospitals, but not at
nonteaching hospitals after the introduction of work hour restrictions [37].
ADHERENCE TO PROTOCOLS Very few specific interventions that are commonly used in the NCCU have been demonstrated to improve outcomes in large randomized trials. Most treatments recommended by international guidelines are based on relatively low-quality evidence that is derived primarily from observational studies or based on physiological principles [38–41]. For example, it is common practice to avoid hypotension or derangements in the partial pressure of oxygen or carbon dioxide [42,43]. Even mild abnormalities in core body temperature and serum glucose or sodium concentration are treated expeditiously [44–46]. Electroencephalography is used liberally to detect and treat nonconvulsive seizures [47]. Although it may be difficult to prove that any one of these interventions makes a difference on its own, it is possible that in combination they have a powerful effect. Avoidance of ‘secondary’ neurological insults is the underlying principle used in neurocritical care protocols, which essentially function as a checklist for ‘best practice’.
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Neuroscience
Study name
Outcome
Yes/Total
Odds ratio and 95% CI
NCC
No NCC
p-Value
Warme
Poor outcome
37/72
33/49
0.083
Mirski
Poor outcome
24/78
26/50
0.017
Elf
Poor outcome
34/154
38/72
0.000
Patel
Poor outcome
68/202
37/83
0.084
Suarez
Poor outcome
512/1180
551/1201
0.222
Varelas
Poor outcome
516/1279
525/1087
0.000
Lerch
Poor outcome
13/39
13/23
0.127
Lott (ICH)
Poor outcome
3110/5993
3459/5875
0.000
Lott (IS)
Poor outcome
908/1446
1968/3101
0.663
Palminteri
Poor outcome
62/164
48/123
0.833
Samuels
Poor outcome
245/386
237/317
0.001
Knopf
Poor outcome
722/1372
493/724
0.000
Kramer
Poor outcome
1444/2390
730/1107
0.002
Pineda
Poor outcome
20/60
33/63
0.034
Varelas (SE)
Poor outcome
36/46
94/122
0.867
Burns
Poor outcome
30/37
24/37
0.121
7781/14985
8309/14034
0.000
0.1
0.2
0.5
Favors NCC
1
2
5
10
Favors control
Meta analysis
FIGURE 2. Observational studies comparing the proportion of patients developing poor outcomes between specialty neurological ICUs and alternative models of care.
In several studies that observed improved outcomes with neurocritical care, the primary ‘intervention’ was a comprehensive protocol [13 ,48,49]. A recent systematic review assessed studies comparing the use of ‘management protocols’ with ‘standard’ care among patients with TBI and reported that the use of protocols was associated with reduced mortality and more favorable neurological recovery [50 ]. Compliance with Brain Trauma Foundation guidelines has also been linked with improved outcomes in some studies [51–53]. &
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LENGTH OF STAY AND WITHDRAWAL OF LIFE-SUSTAINING INTERVENTIONS Although some single-center studies suggest the opposite [54,55], much of the data indicate that ICU length of stay is longer and resource use more intensive when patients are cared for in a NCCU [10,12 ,13 ,16,17,56]. Damian et al. [12 ] found that adjustment for length of stay modified the impact of the type of ICU on hospital mortality. In a population-based study showing improved outcomes over time, length of ICU stay also increased &&
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significantly [14 ]. It is possible that longer length of stay is a marker of a more aggressive approach to patient care [56], or a more cautious disposition toward withdrawal of life-sustaining interventions. Only a small and declining proportion of NCCU patients progress to brain death [15 ]. Unanticipated cardiac arrests after admission to the ICU are rare. In most cases of mortality, death occurs after withdrawal of life-sustaining interventions, primarily mechanical ventilation, based on the perception that the prognosis for a favorable neurological recovery is poor [57–59]. Physicians usually initiate conversations about limitations in care [60]. If the best possible functional or cognitive outcome is one that would not be acceptable to a patient, then withdrawal of life-sustaining interventions may be entirely appropriate and necessary [61]. However, accurate outcome prediction is difficult [62]. Clinicians’ perceptions about prognosis, and in turn their recommendations to patients’ families, may be heterogeneous and influenced by factors other than just patient preferences or the severity of brain injury. Physician experience may be one such factor [63,64 ]. In a Canadian survey about the prognosis &
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of TBI patients, neurologists (who were the least likely to be involved in the care of such patients) were considerably more pessimistic than intensivists or neurosurgeons [64 ]. Another study using a clinical vignette involving a patient with anoxic brain injury reported that recommendations on life-support withdrawal were influenced by physician age and experience, years in practice, and whether or not they provided long-term follow-up for patients [65]. Some studies suggest that physicians are generally more pessimistic than is justified by existing information [66,67]. Unfortunately, available tools to aid in the prediction of long-term prognosis are imperfect [68]. Recent data demonstrate that there is significant variability in the frequency and timing of withdrawal of life-sustaining therapies between institutions [69]. One multicenter study observed that tracheostomies are more likely in NCCUs, which may suggest a greater reluctance toward treatment withdrawal [56]. The best evidence for improved outcomes in NCCUs comes from studies of ICH patients [10,11,12 ], in which the concept of treatment withdrawal leading to ‘self-fulfilling prophecy’ has been best described [66,70–72]. Nevertheless, despite these observations, it remains unclear whether there are systematic differences in withdrawal of life-support practices based on the type of ICU where patients receive their care. &
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MULTIMODAL NEUROLOGICAL MONITORING In studies that compare outcomes of TBI patients in neurological and general ICUs, the use of ICP monitoring was one of several interventions that were more common in neurological units [48,49,69]. In general, increased use of ICP monitoring, used with a detailed management protocol, has been associated with more favorable outcomes in observational studies, although results are somewhat variable [50 ,73]. The Benchmark Evidence from South American Trials : Treatment of Intracranial Pressure study was a randomized trial performed in general ICUs in South America that compared two management protocols, one with and the other without ICP monitoring. There was a trend toward lower early mortality with ICP monitors, but 6-month outcomes were similar [74]. There were several study limitations, which have been discussed at length in the study correspondence and subsequent editorials. Importantly, ICP monitoring differed from the way it is used in many NCCUs, so limiting the study’s external validity. For example, monitoring was provided for a median of only 3.6 days (interquartile range &
2.0–6.6 days), even though intracranial hypertension frequently persists longer than this [75,76]. Patients without monitors received more osmotic therapy and hyperventilation, whereas the pressuremonitored group received more barbiturates, a therapy that is now infrequently used at many centers. Furthermore, cerebrospinal fluid drainage was almost never used and almost one-third of the nonmonitored patients underwent early decompressive craniectomy, which in turn may have attenuated any benefit from ICP monitoring. Neurocritical care patients are heterogeneous. Even within a particular diagnostic subgroup like TBI, it seems unlikely that targeting a single treatment threshold in all patients (e.g. ICP < 20 mmHg) represents the optimal approach. Increasingly, neurointensivists integrate ICP and cerebral perfusion pressure with other information, including neuroimaging, intracranial compliance, cerebral blood flow autoregulation and information derived from other modes of neurological monitoring before making treatment decisions [77–80]. Indeed, the theoretical advantage of multimodal monitoring is individualization of therapeutic targets based on the specific characteristics of a patient. Existing publications assessing multimodal monitoring, for example with use of both ICP and brain tissue oxygen monitors, have reached conflicting conclusions, with some studies suggesting benefit and others indicating either no effect or even harm [81–85]. The efficacy of brain tissue oxygen monitoring is currently being assessed in the Brain Tissue Oxygen Monitoring in Traumatic Brain Injury (BOOST 2) trial [86]. It seems obvious that the usefulness of any monitoring device depends on what clinicians do with the acquired information. A potential advantage of multimodal monitoring may be that it promotes awareness of the cerebral effects of common day-to-day interventions in the ICU. For example, using multimodal monitoring, researchers have reported deleterious effects attributable to sedation interruption [87,88], fiberoptic bronchoscopy [89], percutaneous tracheostomy insertion [90], and patient transport for diagnostic procedures [91]. Intensivists may perform or facilitate these interventions without any knowledge of the cerebral implications. NCCUs usually have a ‘culture’ that strongly emphasizes neuroprotection, with careful consideration of the cerebral effects of any intervention.
CONCLUSION In summary, a large body of evidence demonstrates that outcomes are improved when braininjured patients are cared for in NCCUs. A variety
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of organizational models have been used to effectively deliver such care. Future studies should seek to better understand which specific practices are most important and whether or how the observed relationship is causal. Much research is required to clarify how management protocols can be optimized to further reduce mortality and maximize neurological recovery. Acknowledgements None. Conflicts of interest This manuscript has not been published previously. It has not been submitted to another journal. The authors have no conflicts of interest to declare.
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