2. • Brain edema after ICH can be divided into
perihematomal edema (PHE) and
intrahematomal edema.
• Most patients could survive the initial injury
of smaller hemorrhage, but the secondary
injury may result in severe neurological
deficits and even death
3. Mechanism of Edema in ICH
• Brain edema increases in the first 24 h
progressively and increases rapidly 3 days after
onset, reaches its initial peak at the 4th or the 5th
day and remains elevated slowly until 9-14 days
and then decreases [12].
• PHE develops in response to clot retraction and
hydrostatic pressure change [13], mass effect,
thrombin formation, erythrocyte lysis, Hb toxicity,
complement activation, plasma proteins leakage
and blood-brain barrier (BBB) disruption [5].
9. Mechanisms of secondary brain injury after ICH.
MLS - midline shift; IVH - intraventricular
hemorrhage
10. • Prognostic score=(10×admission Glasgow com
a score)−age (years)−[0.64×volume (ml)]Progn
ostic score=(10×admission Glasgow coma scor
e)−age (years)−[0.64×volume (ml)]
• A score > 27.672 was used as a cutoff point for
a good prognosis.
• Predicted good outcome eGOS = 5–8.
17. 2020 Update of the Decompressive
Craniectomy Recommendations
• Level IIA–to improve mortality and overall outcomes
• 1. NEW–Secondary DC performed for late refractory ICP elevation is
recommended to improve mortality and favorable outcomes.
• 2. NEW–Secondary DC performed for early refractory ICP elevation
is not recommended to improve mortality and favorable
outcomes†.
• 3. A large frontotemporoparietal DC (not less than 12 × 15 cm or
15 cm in diameter) is recommended over a small
frontotemporoparietal DC for reduced mortality and improved
neurological outcomes in patients with severe TBI.
• Level IIA–for ICP control
• 4. NEW–Secondary DC, performed as a treatment for either early or
late refractory ICP elevation, is suggested to reduce ICP and
duration of intensive care, though the relationship between these
effects and favorable outcome is uncertain.
18. Differences between the randomized
controlled trials for decompressive
craniectomy in traumatic brain injury
19. Surgical trial in traumatic ICH (STITCH)
• The STITCH Trauma Trial is assessing whether surgery makes a
difference for patients with traumatic ICH and contusion.
Mendelow et al.39) in 2015, reported international multicenter,
patient-randomized, parallel-group trial compared early surgery
(hematoma evacuation within 12 hour of randomization) with initial
conservative treatment (subsequent evacuation allowed if deemed
necessary). Patients who enrolled in this trial were randomized
within 48 hour of TBI. Patients who had more than two
intraparenchymal hemorrhage of 10 cc or more and have an EDH or
SDH that need surgery were excluded in this trial. The treatment
outcomes were obtained by postal questionnaires after 6 months.
Patients were randomized to early surgery group and 85 patients
were in initial conservative group. The treatment outcome were 30
of 82 patients in early surgery group (37%) had an unfavorable
outcome and 40 of 85 patients in initial conservative group (47%)
had an unfavorable outcome with an absolute benefit of 10.5%. The
result showed significant more deaths in the first 6 months in the
initial conservative treatment group (p=0.006).
All of inflammation, thrombin activation and red blood cell (RBC) lysis production contribute to BBB disruption resulting in edema formation, and it can be diversified into 3 phases: (1)clot retraction could force the serum into the perihematomal space to form vasogenic edema (1 h after ICH; fig. 1), (2) inflammation (fig. 2) and thrombin activation (fig. 3)-related cytotoxic brain edema through clotting cascade (peaking at 1-2 days), and (3) erythrocyte lysis and Hb toxicity-related injury (delayed edema formation at about day 3; fig. 4) [14].
Intrahematomal edema is mainly caused by tension hematoma. Tension hematoma is related to the formation of capsule-like granulation tissue during the absorption of a hematoma. The capsule-like granulation can limit the absorption of liquified hematoma and cytotoxic substance. Subsequently, the oncotic pressure inside the hematoma increases and the infiltration of perihematoma water and plasma increases the tension inside the capsule progressively. Additionally, blood may leak repeatedly from the abundant capillaries contained in the granulation tissue resulting in hematoma enlarging [15].
Both elevated oncotic pressure of perihematoma space due to the infiltration of blood components from hematoma and BBB disruption caused by inflammation, thrombin cascade and erythrocyte lysis products can aggravate vasogenic edema. However, oxidative stress induced by vasogenic edema, and release of cytotoxic substance could induce cytotoxic edema. So, vasogenic edema and cytotoxic edema interact with each other and lead to a vicious circle.
Fig. 1 | Haemoglobin scavenging pathways in humans. Multiple receptor mediated-pathways can prevent the toxicity of haemoglobin and its breakdown products haem and iron. Red blood cells (RBCs) can be directly phagocytosed following detection by the CD36 receptor on macrophages (step 1). Free haemoglobin dimers can be captured by haptoglobin, and the haptoglobin–haemoglobin complex can be taken up by macrophages via CD163 (step 2). CD163 can be shed from the cell surface after subarachnoid haemorrhage owing to the action of the enzyme disintegrin and metalloproteinase domain-containing protein 17 (ADAM17), and this process might reduce the efficiency of haemoglobin scavenging. In the phagolysosome, haemoglobin is then broken down to release haem, which is in turn broken down by haem oxygenases to generate iron (step 3). Similarly, free extracellular haem can be captured by haemopexin and transported into macrophages via CD91 (step 4), where it is also broken down to produce free iron (step 3). The resulting iron is transported from macrophages via the ferroportin 1 (FPN1; also known as SLC40A1) channel (step 5). HRG1, haem-responsive gene 1 protein homologue (also known as SLC48A1); NADPH–CPR, NADPH–cytochrome P450 reductase; sCD163, soluble CD163.
Blood components with direct neurotoxic effects, their concentration in whole blood, the concentration needed to achieve half-maximal neuronal death (LD50) in cultured neurons, and their blood concentration relative to their LD50.
Escalation management for controlling ICP in TBI patients with or without inv-ICP monitoring. Escalation of care in patients with HICP or neuroworsening/radiological impairment [Modified from Hawryluk et al. (9) and Carney et al. (4)]. inv-ICP, invasive intracranial pressure; ETI, endotracheal intubation; MV, mechanical ventilation; CPP, cerebral perfusion pressure; Hb, hemoglobin; PaCO2, partial pressure of carbon dioxide; CSF, cerebral spinal fluid; SpO2, peripheral saturation of oxygen; HOB, head of the bed; CT, computed tomography; HICP, intracranial hypertension; PbtO2, brain tissue oxygen tension; EVD, external ventricular drainage; EEG, electroencephalography; FiO2, fraction of inspired oxygen; MAP, mean arterial pressure; PaO2, partial pressure of oxygen; GCS, Glasgow coma scale.
Figure 3. De-escalation management after controlling intracranial hypertension in TBI patients with or without inv-ICP monitoring. De-escalation management for controlling intracranial hypertension basing on available current evidences [Modified from Stocchetti et al. (3), Hawryluk et al. (9) and Carney et al. (4)]. inv-ICP, invasive intracranial pressure; CPP, cerebral perfusion pressure; Hb, hemoglobin; PaCO2, partial pressure of carbon dioxide; CSF, cerebral spinal fluid; CT, computed tomography; HICP, intracranial hypertension; EVD, external ventricular drainage; NWT, neurological wake-up test.
Decompressive Craniectomy (DC)
Decompressive craniectomy (DC) consists in the removal of a portion of skull in order to treat refractory HICP and represents the most aggressive step of the “staircase approach” (103). When the bone flap is not replaced after surgery for the evacuation of an intracranial mass lesion, DC is named “primary,” while it is considered “secondary” when DC is performed later after other treatments have failed (104). DC can be performed as a large frontal-temporal-parietal flap (at least 12 × 15 cm diameter) (104) or as a bifrontal flap; both techniques have shown an efficacy close to 100% for ICP control (1–4, 9, 13, 99, 105). However, the optimal indications, technical aspects, and timing for DC are still debated. Two major multicenter randomized controlled trials (RCTs) comparing decompressive craniectomy with medical management tried to provide guidance to clarify timing and indications of DC: Decompressive Craniectomy in Patients with Severe Traumatic brain Injury (DECRA) and Trial of Decompressive Craniectomy for Traumatic Intracranial Hypertension (RESCUEicp) (2, 13). The DECRA trial showed a similar rate of mortality between medical and surgical cohorts, with a higher rate of unfavorable neurologic outcomes in the surgical group. On the other hand, the RESCUEicp study observed lower mortality for DC, but higher rates of vegetative state, as well as lower and upper severe disability at 6 months, in comparison to medical therapy (2). A key difference between the two studies was that DECRA investigated the effects of DC for early HICP, while the effects of DC for late HICP were analyzed by RESCUEicp (104). In fact, DECRA included patients with HICP (> 20 mmHg) for 15 min over a 1-h period although the tier 1 therapies within the first 72 h after trauma, while RESCUEicp included patients with HICP (> 25 mmHg) for 1 to 12 h despite the tiers 1 and 2 therapies within the first 10 days after TBI (2, 13). Therefore, the interpretations and recommendations extrapolated from these studies should refer to early and late refractory HICP. A recent update on DC by the Brain Trauma Foundation (104), based on the RESCUEicp and DECRA findings, developed Level IIA recommendations, suggesting that secondary DC for early refractory HICP is not recommended to improve mortality and outcome, while is suggested in case of late refractory HICP. Otherwise, DC performed both in early and late refractory HICP is recommended to reduce ICP and ICU length-of-stay. Moreover, Authors observed that bifrontal DC (the technique used in the DECRA trial) is effective to reduce ICP and ICU-stay, but it is not recommended to improve outcome and mortality if performed in accordance with the DECRA inclusion criteria. Besides, the 2020 update of the BTF guidelines (104) concluded that a frontal-temporal-parietal DC (12 × 15 cm) is recommended over a small flap for mortality and outcome improvement after severe TBI (106, 107). Many other studies analyzed the use of DC in severe TBI and its implications for long-term neurological outcome, confirming its efficacy for ICP control and reduction of mortality, but increasing long-term disability (108–115). The socioeconomic context, patients' priorities, and the recognition of clinical and radiological prognostic factors (for which further validation studies are needed) should be considered before indicating DC.
