Study flow chart
Please see Report Supplementary Material 2.
Recruitment
A total of 386 patients from 37 sites in 10 countries were recruited to the observation data set between 8 September 2014 and 29 April 2019 (UK 22, India 4, Canada 3, USA 2, Spain 1 Malaysia 1, Greece 1, Germany 1, Australia 1, Hungary 1).
Numbers analysed
A total of 3566 patients were screened for eligibility, with 386 enrolled in the observed arm. There were 141 in the craniotomy arm and 245 in the DC arm.
Baseline data
Behavioural history, demography and coagulation history
Patients having DC were 17 years younger on average, less likely to have insurance, less likely to have been on anticoagulants or aspirin and more likely to have had a GCS between 3 and 8 (Table 11).
| Characteristics of the observation cohort patients at baselinea | |||
|---|---|---|---|
| Characteristic | Observed craniotomy (N = 141) | Observed DC (N = 245) | χ2, p-values (age = Mann–Whitney U-test) |
| Age – year | 59.2 ± 15.9 | 42.4 ± 15.5 | < 0.0001 |
| Male sex – number/total number (%) | 101/140 (72.1) | 195/244 (79.9) | 0.081 |
| Any antithrombotic medication – number/total number (%)b | 41/122 (33.6) | 14/225 (6.2) | < 0.0001 |
| Presence of major extracranial injury requiring admission — number/total number (%) | 54/140 (38.6) | 127/245 (51.8) | 0.012 |
| GCS 3–8c | 57/128 (44.5) | 156/231 (67.5) | < 0.0001 |
| Initial CT brain findings | |||
| Presence of midline shift > 5 mm – number/total number (%) | 120/139 (86.3) | 206/244 (84.4) | 0.615 |
| Compression/absence of basal cisterns – number/total number (%) | 107/139 (77.0) | 212/243 (87.2) | 0.009 |
| Presence of parenchymal contusions < 25 cc – number/total number (%) | 50/139 (36.0) | 166/242 (68.6) | < 0.0001 |
Accident details and pre-hospital events
Almost all injuries were closed-head injuries (96%). Patients undergoing DC were more likely to have extracranial injury requiring admission. They were more likely to have been injured as a motorcyclist and less likely to have been injured in an incidental fall. Their experience of pre-hospital events was similar. (Combining suicide, other non-intentional injuries with other gives p < 0.0001 Table 12.)
| Observed craniotomy (n = 141) | Observed DC (n = 245) | χ2 – p-values | ||
|---|---|---|---|---|
| Injury mechanism | Motor vehicle occupant | 9 (6%) | 23 (9%) | |
| Cyclist | 2 (1%) | 12 (5%) | ||
| Incidental fall | 90 (64%) | 93 (38%) | ||
| Motor bike | 0 | 39 (16%) | ||
| Suicide attempt | 0 | 3 (1%) | ||
| Other non-intentional | 2 (1%) | 1 (–%) | ||
| Pedestrian | 9 (6%) | 27 (11%) | ||
| Violence/assault | 10 (7%) | 27 (11%) | ||
| Other | 18 (13%) | 20 (8%) | ||
| Not available | 1 | |||
| Pre-hospital event hypoxia (PO2 < 8 kPa/SpO2 < 90%) | Yes | 11 (8%) | 17 (7%) | 0.575 |
| Suspected | 14 (10%) | 25 (10%) | ||
| No | 91 (65%) | 145 (60%) | ||
| Unknown | 24 (17%) | 56 (23%) | ||
| Not available | 1 | 2 | ||
| Pre-hospital event hypotension (SBP < 90 mmHg) | Yes | 7 (5%) | 18 (7%) | 0.091 |
| Suspected | 9 (6%) | 13 (5%) | ||
| No | 106 (76%) | 159 (65%) | ||
| Unknown | 18 (13%) | 54 (22%) | ||
| Not available | 1 | 1 | ||
| Pre-hospital event hypothermia (temp < 35 C) | Yes | 9 (6%) | 17 (7%) | 0.383 |
| Suspected | 3 (2%) | 2 (1%) | ||
| No | 96 (69%) | 152 (63%) | ||
| Unknown | 32 (23%) | 71 (29%) | ||
| Not available | 1 | 3 | ||
| Pre-hospital event cardiac arrest | Yes | 6 (4%) | 3 (1%) | 0.074 |
| No | 127 (95%) | 234 (96%) | ||
| Unknown | 1 (1%) | 6 (2%) | ||
| Not available | 7 | 2 | ||
| Pre-hospital event seizures | Yes | 21 (15%) | 19 (8%) | 0.072 |
| No | 101 (72%) | 187 (76%) | ||
| Unknown | 18 (13%) | 39 (16%) | ||
| Not available | 1 | |||
| Pre-hospital event clinical deterioration | Yes | 50 (36%) | 66 (27%) | 0.197 |
| No | 79 (56%) | 154 (63%) | ||
| Unknown | 11 (8%) | 24 (10%) | ||
| Not available | 1 | 1 | ||
| Pre-intubation GCS | 3–8 | 57 (45%) | 156 (68%) | < 0.0001 |
| 9–15 | 71 (55%) | 75 (32%) | ||
| Not available | 13 | 14 | ||
| Pupil reactivity | Neither pupil reactive | 15 (11%) | 51 (21%) | 0.014 |
| At least one reactive | 115 (82%) | 173 (71%) | ||
| Both untestable | 0 () | 6 (2%) | ||
| Unknown | 11 (8%) | 15 (6%) | ||
Medical history
Patients treated by craniotomy had more medical history (Table 13).
| Observed craniotomy (n = 141) | ObservedDC(n = 245) | χ2 – p-values | ||
|---|---|---|---|---|
| Any medical history | No | 19 (14%) | 136 (57%) | < 0.0001 |
| Yes | 116 (84%) | 89 (37%) | ||
| Unknown | 3 (2%) | 15 (6%) | ||
| Missing | 3 | 5 | ||
| n = 135 | n = 225 | |||
| Conditions | Cardiovascular | 60 (44%) | 21 (9%) | < 0.0001 |
| Endocrinological | 28 (21%) | 16 (7%) | < 0.0001 | |
| Hearing/vision | 5 (4%) | 5 (2%) | 0.408 | |
| Gastrointestinal | 16 (12%) | 10 (4%) | 0.009 | |
| Haematological | 3 (2%) | 1 (–%) | 0.119 | |
| Liver | 7 (5%) | 5 (2%) | 0.129 | |
| Musculoskeletal | 5 (4%) | 6 (3%) | 0.580 | |
| Respiratory | 20 (15%) | 9 (4%) | < 0.0001 | |
| Neurological | 29 (21%) | 22 (10%) | 0.002 | |
| Oncological | 16 (12%) | 7 (3%) | 0.001 | |
| Psychiatric | 27 (20%) | 25 (11%) | 0.020 | |
| Renal | 14 (10%) | 5 (2%) | 0.001 | |
| Other | 59 (44%) | 39 (17%) | < 0.0001 | |
Please see Appendix 10 for admission vital signs table.
Glasgow Outcome Scale-Extended outcomes
Six-month Glasgow Outcome Scale-Extended scores
| Observed craniotomy (n = 141) | Observed DC (n = 245) | Total observed (n = 386) | ||
|---|---|---|---|---|
| GOSE at 6 months | Dead | 27 (22%) | 80 (38%) | 107 (32%) |
| Vegetative | 1 (1%) | 10 (5%) | 11 (3%) | |
| Lower severely disabled | 34 (28%) | 57 (27%) | 91 (27%) | |
| Upper severely disabled | 21 (17%) | 19 (9%) | 40 (12%) | |
| Lower moderately disabled | 10 (8%) | 17 (8%) | 27 (8%) | |
| Upper moderately disabled | 8 (7%) | 17 (8%) | 25 (7%) | |
| Lower good recovery | 8 (7%) | 5(2%) | 13 (4%) | |
| Upper good recovery | 15 (12%) | 6 (3%) | 21 (6%) | |
| Missing | 17 | 34 | 51 | |
| Outcome | OR | 95% CI | p-value | Number of cases in analysis |
| 6 months, ordinal | 0.430 | 0.287 to 0.642 | < 0.0001 | 335 |
| 6 months, dichotomy | 0.435 | 0.275 to 0.689 | 0.0003 | 335 |
Twelve-month Glasgow Outcome Scale-Extended scores
| Observed craniotomy (n = 141) | Observed DC (n = 245) | Total observed (n = 386) | ||
|---|---|---|---|---|
| GOSE at 12 months | Dead | 29 (22%) | 86 (38%) | 115 (32%) |
| Vegetative | 3 (2%) | 9 (4%) | 12 (3%) | |
| Lower severely disabled | 25 (29%) | 47 (21%) | 72 (20%) | |
| Upper severely disabled | 20 (16%) | 25 (11%) | 45 (13%) | |
| Lower moderately disabled | 7 (5%) | 12 (5%) | 19 (5%) | |
| Upper moderately disabled | 15 (12%) | 22 (10%) | 37 (10%) | |
| Lower good recovery | 13 (10%) | 5 (2%) | 18 (5%) | |
| Upper good recovery | 17 (13%) | 20 (9%) | 37 (10%) | |
| No follow-up possible | 3 | 3 | 6 | |
| Known alive but lost to follow-up | 9 | 16 | 25 | |
| Outcome | OR | 95% CI | p-value | Number of cases in analysis |
| 12 months, ordinal | 0.476 | 0.323 to 0.702 | 0.0002 | 356 |
| 12 months, ordinal adjusteda | 0.387 | 0.237 to 0.632 | 0.0001 | 332 |
| 12 months, dichotomy | 0.465 | 0.300 to 0.722 | 0.0006 | 356 |
| 12 months, dichotomy adjusteda | 0.329 | 0.178 to 0.608 | 0.0004 | 332 |
Case report form stage 1 results
Treatment received
Of the craniotomy patients, three mention use of floating brain flap, and one of the DC patients mention bifrontal DC. There were seven ‘Other’ reasons for not randomising in the craniotomy group: age (1), system failure (2), family refuse randomisation (2), recovered from stroke (1), infection of scalp (1) (Table 16).
There were three ‘Other’ reasons for not randomising in those that had DC: skull fracture (2), not expected to survive (1).
| Observed craniotomy | Observed DC | Total | ||
|---|---|---|---|---|
| Number of patients | 141 | 245 | 386 | |
| N = 139 | N = 244 | N = 383 | ||
| Reason not randomised | Intraoperative brain swelling | 6 (4%) | 201 (82%) | 207 (54%) |
| Brain relaxed | 89 (64%) | 7 (3%) | 96 (25%) | |
| Anticipated swelling | 1 (1%) | 18 (7%) | 19 (5%) | |
| Trial staff not available | 15 (11%) | 5 (2%) | 20 (5%) | |
| Other | 28 (20%) | 13 (5%) | 41 (11%) | |
| Not considered for trial | 6 (4%) | 4 (2%) | 10 (3%) | |
| No equipoise/surgeon decision | 15 (11%) | 6 (2%) | 21 (5%) | |
| Other | 7 (5%) | 3 (1%) | 10 (3%) | |
| Not recorded | 2 | 1 | 3 | |
Computed tomography scan results
Patients with parenchymal lesions or traumatic subarachnoid haemorrhage (SAH) were more likely to have DC. Please see Appendix 10 for full table.
Pre-intubation Glasgow Coma Scale and pupil reactivity
Patients receiving DC have lower GCS scores (Mann–Whitney U-test p < 0.0001) and are more likely to have neither pupil reactive (than at least one reactive) (p = 0.009). Please see Appendix 10 for full table.
Surgery details and postoperative destination
There was no difference in the location of the ASDH between the treatment groups (p = 0.630).
There were no differences between the treatment groups in terms of the type of skin incision, with 89% reverse question mark (p = 0.695), or in the size of the bone flap [with a mean of cm (± cm)].
A drain was used in 78% of patients and was usually subgaleal (55%) rather than subdural (23%) [no difference between treatments (p = 0.718)]. Intracranial monitoring devices were used in 67% of patients, and most (78%) being located ipsilateral to the ASDH. They were more likely to be ipsilateral in craniotomy (p = 0.004). For the patients who underwent DC, the bone flap was either stored inside the body (34%) or disposed of (35%) (Table 17).
There were more likely to be intraoperative complications in DC (χ2 p = 0.010). There were no differences between treatment groups in the destination from the operating theatre (χ2 p = 0.984).
| Observed craniotomy (n = 141) | Observed DC (n = 245) | χ2 – p-values | ||
|---|---|---|---|---|
| Type of skin incision | Reverse question mark | 127 (90%) | 215 (88%) | 0.695 |
| T-shaped | 1 (1%) | 4 (2%) | ||
| Other | 13 (9%) | 25 (10%) | ||
| Not available | 1 | |||
| Drain used | Subdural | 34 (24%) | 52 (21%) | 0.718 |
| Subgaleal | 74 (53%) | 138 (57%) | ||
| None | 32 (23%) | 52 (21%) | ||
| Not available | 1 | 3 | ||
| Size of bone flap | Mean (SD) | 12.1(1.8) | 13.2 (2.0) | |
| Median | 12 | 13 | ||
| IQR | 2 | 3 | ||
| Minimum, maximum | 7, 20.3 | 1.2, 20.0 | ||
| Not available | 11 | 6 | ||
| Location of ASDH | Left | 65 (46%) | 120 (49%) | 0.630 |
| Right | 75 (54%) | 125 (51%) | ||
| Not available | 1 | |||
| Dura closure | Open | 43 (31%) | 108 (44%) | |
| Closed | 76 (54%) | 20 (8%) | ||
| Duraplasty | 18 (13%) | 107 (44%) | ||
| Other | 3 (2%) | 9 (4%) | ||
| Not available | 1 | 1 | ||
| Other haematoma evacuateda | No | 121 (86%) | 187 (77%) | |
| Yes | 20 (14%) | 57 (23%) | ||
| Not available | 5 (4%) | 1 | ||
| Intracerebral | 5 (4%) | 15 (6%) | ||
| Extradural | 12 (9%) | 10 (4%) | ||
| Contusions | 2 (1%) | 32 (13%) | ||
| Other | 4 (2%) | |||
| Intracranial monitoring device | No | 43 (30%) | 86 (35%) | |
| Yes, EVD | 2 (2%) | 8 (3%) | ||
| Yes, epidural | 41 (29%) | 35 (14%) | ||
| Yes, subdural/subarachnoid | 4 (3%) | 3 (1%) | ||
| Yes, parenchymal | 44 (31%) | 104 (42%) | ||
| Other | 7 (5%) | 9 (4%) | ||
| Location of the monitoring device | Ipsilateral to ASDH | 83 (87%) | 112 (72%) | |
| Contralateral to ASDH | 12 (13%) | 44 (28%) | ||
| Not available | 3 | 3 | ||
| Not applicable | 43 | 86 | ||
| Transfer destination after operation | ICU/neurocritical care unit (NCCU) | 129 (91%) | 224 (91%) | 0.984 |
| NSU/ward | 12 (9%) | 21 (9%) | ||
| Other | 0 | 0 | ||
Stage 2 case report form results
Glasgow Coma Scale and discharge details
Stage 2 GCS and discharge details for first stay of any patient in ITU. Table 18 includes all those who were admitted to neurocritical care unit (NCCU) from the operating theatre.
| Observed craniotomy (n = 129) | Observed DC (n = 224) | |||
|---|---|---|---|---|
| Discharge destination from ICU/NCCU | Dieda | 15 (12%) | 47 (21%) | χ2 – p-value 0.109 |
| NSU | 99 (77%) | 160 (71%) | ||
| Different hospital | 12 (9%) | 16 (7%) | ||
| Other | 2 (2%) | 1 (1%) | ||
| Missing data | 1 | |||
| Number discharged from ICU/NCCU | (n = 113) | (n = 177) | ||
| GCS total score (discharge from ICU/NCCU) | Scoring 3 | 2 (2%) | 3 (3%) | Mann–Whitney U-test |
| Scoring 4 | 1 (1%) | 3 (3%) | p-value 0.004 | |
| Scoring 5 | 0 | 0 | ||
| Scoring 6 | 0 | 2 (2%) | ||
| Scoring 7 | 0 | 1 (1%) | ||
| Scoring 8 | 3 (3%) | 3 (3%) | ||
| Scoring 9 | 2 (2%) | 8 (7%) | ||
| Scoring 10 | 4 (4%) | 9 (8%) | ||
| Scoring 11 | 6 (6%) | 11 (9%) | ||
| Scoring 12 | 8 (8%) | 7 (6%) | ||
| Scoring 13 | 7 (7%) | 13 (11%) | ||
| Scoring 14 | 32 (33%) | 38 (32%) | ||
| Scoring 15 | 31 (31%) | 21 (18%) | ||
| Number unknown | 16 | 1 | ||
| Number untestable | 1 | 51 | ||
| Number missing | 6 | |||
Stage 3 case report form results
Neurosurgical interventions within 14 days of index surgery
These are recorded on the discharge from NSU CRF. The information is not recorded for 84 patients (24 craniotomy and 60 DC) (including most of the patients who died in ICU or were discharged from there to a different hospital) (Table 19).
| Observed craniotomy (n = 141) | Observed DC (n = 245) | Total observed (n = 386) | ||
|---|---|---|---|---|
| Neurosurgical interventions after index surgery | Yes | 17 (15%) | 15 (8%) | 32 (11%) |
| No | 100 (85%) | 170 (92%) | 270 (89%) | |
| Missing | 24 | 60 | 84 | |
| Number of interventions | 1 | 16 | 13 | 29 |
| 2 | 0 | 2 | 2 | |
| 3 | 1 | 0 | 1 | |
| 4 | 0 | 0 | 0 | |
| Total number of interventions | N = 19 | N = 17 | N = 36 | |
| Intervention | Craniectomy | 5 (26%) | 0 | 5 (14%) |
| Cranioplasty | 0 | 0 | 0 | |
| SDH evacuation | 3 (16%) | 3 (18%) | 6 (17%) | |
| EDH evacuation | 4 (21%) | 2 (12%) | 6 (17%) | |
| ICH evacuation | 0 | 1 (6%) | 2 (3%) | |
| EVD inserted | 1 (5%) | 3 (18%) | 4 (11%) | |
| Shunt placement | 0 | 0 | 0 | |
| ICP monitor | 2 (11%) | 3 (18%) | 5 (14%) | |
| Wound revision | 2 (11%) | 3 (18%) | 5 (14%) | |
| Other | 2 (11%) | 2 (12%) | 4 (11%) | |
Length of stay of all patients discharged from neurosurgical unit or intensive care unit
Among patients who were discharged alive, those who had had DC as initial surgery had a longer stay (Mann–Whitney U-test p = 0.007). There was no difference in time to death for those who died in hospital (Mann–Whitney U-test p = 0.449) (Table 20).
| Observed craniotomy (n = 141) | Observed DC (n = 245) | Total observed (n = 386) | ||
|---|---|---|---|---|
| Discharge destination from NSU | Died in hospital | 21 | 61 | 82 |
| Discharged from NSU | 118 | 184 | 302 | |
| Missing (still on ward at 12 months) | 2 | 0 | 2 | |
Status and destination at discharge from any part of the neurosurgical unit
Discharge destination (combining nursing home, unknown and other) (p = 0.014). GCS total χ2 = 0.056 (3 category) (Mann–Whitney U-test on full score p = 0.048). Please see Appendix 10 for full table.
Stage 4 case report form results
Stage 4 cranioplasty and shunt use
Details about cranioplasty are recorded at 12 months.
| Observed craniotomy (n = 141) | Observed DC (n = 245) | p-values (associated test in table footer) | ||
|---|---|---|---|---|
| Had DC before 12 months | Yes | 11 (8%) | 233 (100%) | |
| No | 120(92%) | 0 | ||
| Missing | 10 | 12 | ||
| Had cranioplasty by 12 months | (n = 11) | (n = 233) | 0.466 | |
| Yes | 7 (64%) | 120 (52%) | ||
| No | 4 (36%) | 109 (48%) | ||
| 4 | ||||
| Had a cranioplasty | (n = 7) | (n = 120) | ||
| Material | Autograft | 2 (29%) | 53 (46%) | |
| Non-metallic | 1 (14%) | 22 (19%) | ||
| Metallic | 4 (57%) | 39 (34%) | ||
| 6 | ||||
| (n = 141) | (n = 245) | |||
| Did the patient develop hydrocephalus | Yes | 3 (2%) | 13 (6%) | 0.145 |
| No | 123 (98%) | 213 (94%) | ||
| Missing | 15 | 19 | ||
| Did the patient have a shunt | Yes | 1 | 9 | 0.247 |
| No | 2 | 4 | ||
If a patients had a DC, then there was no difference between the allocated groups in whether they had a cranioplasty by 12 months (χ2 p = 0.466) (Table 21).
There was no difference in the rate of hydrocephalus between the two patient treatment groups (χ2 p = 0.145) or in the use of a shunt if they did develop hydrocephalus (Fisher’s exact p = 0.247).
Adverse events: observational
One hundred and twenty-three AEs are reported by 76 (54%) of the 141 patients having craniotomy as initial treatment. The maximum number of events reported for a single patient was 7, and the average number of events reported by those randomised to craniotomy was 0.87. One hundred and sixty-seven AEs were reported by 105 (43%) of the 245 patients having DC as initial treatment. The maximum number of events reported for a single patient in this group was 4, and the average number of events reported by a patient randomised to DC was 0.68. There are no differences in the types of AEs experienced between the two treatment groups (Table 22).
| Event | Observed craniotomy (n = 141) | Observed DC (n = 245) | Total observed (n = 386) |
|---|---|---|---|
| Pneumonia | 46 (33%) | 61 (25%) | 107 (28%) |
| Pneumothorax | 1 (1%) | 4 (2%) | 5 (1%) |
| Atelectasis | 4 (3%) | 2 (1%) | 6 (2%) |
| Aspiration | 5 (4%) | 5 (2%) | 10 (3%) |
| Pleural effusion/empyema | 4 (3%) | 3 (1%) | 7 (2%) |
| Ventilator-related complications | 7 (5%) | 9 (4%) | 16 (4%) |
| Adult respiratory distress syndrome | 1 (1%) | 2 (1%) | 3 (1%) |
| Respiratory failure | 4 (3%) | 3 (1%) | 7 (2%) |
| Need for prolonged mechanical or positive pressure airway ventilation | 9 (6%) | 24 (10%) | 33 (9%) |
| Other respiratory | 4 (3%) | 3 (1%) | 7 (2%) |
| Myocardial infarction | 2 (1%) | 0 | 2 (1%) |
| Arrhythmia | 9 (6%) | 7 (3%) | 16 (4%) |
| Heart failure | 1 (1%) | 1 (–%) | 2 (1%) |
| Angina | 0 | 0 | 0 |
| Pericardial effusion | 0 | 0 | 0 |
| Other cardiac | 1 (1%) | 3 (1%) | 4 (1%) |
| Urinary tract infection | 8 (6%) | 6 (2%) | 14 (4%) |
| Renal failure may require full renal support | 0 | 0 | 0 |
| Renal dysfunction | 3 (2%) | 1 (–%) | 4 (1%) |
| Urinary retention | 1 (1%) | 0 | 1 (–%) |
| Haematuria | 3 (2%) | 2 (1%) | 5 (1%) |
| Other renal | 1 (1%) | 2 (1%) | 3 (1%) |
| Deep-vein thrombosis | 3 (2%) | 3 (1%) | 6 (2%) |
| Pulmonary embolism | 0 | 1 (–%) | 1 (–%) |
| Other thrombosis | 0 | 1 (–%) | 1 (–%) |
| Other | 1 (1%) | 1 (–%) | 2 (1%) |
| Pancreatitis | 0 | 1 (–%) | 1 (–%) |
| Liver failure | 0 | 3 (1%) | 3 (1%) |
| Other | 2 (1%) | 3 (1%) | 5 (1%) |
| Infective diarrhoea or colitis | 1 (1%) | 4 (2%) | 5 (1%) |
| Diarrhoea of other causes | 10 (7%) | 8 (3%) | 18 (5%) |
| Bowel ischaemia | 0 | 1 (–%) | 1 (–%) |
| Ileus | 1 (1%) | 3 (1%) | 4 (1%) |
| Other | 4 (3%) | 2 (1%) | 6 (2%) |
| Wound infection | 0 | 9 (4%) | 9 (2%) |
| Dehiscence | 1 (1%) | 0 | 1 (–%) |
| Other | 1 (1%) | 2 (1%) | 2 (1%) |
| Decubitus ulcer | 0 | 2 (1%) | 2 (1%) |
| Other infections, for example, MRSA | 3 (2%) | 8 (3%) | 11 (3%) |
| Anaesthetic-related complications | 1 (1%) | 1 (–%) | 2 (1%) |
| Anaemia, coagulopathy | 10 (7%) | 15 (6%) | 25 (7%) |
| Pyrexia | 27 (19%) | 59 (24%) | 86 (22%) |
| Septicaemia | 9 (6%) | 10 (4%) | 19 (5%) |
| Hypertension | 2 (1%) | 0 | 2 (1%) |
| Hypotension | 0 | 1 (–%) | 1 (–%) |
| Electrolyte and endocrine disorders | 0 | 3 (1%) | 3 (1%) |
| Dizziness and physical impairment | 6 (4%) | 1 (–%) | 7 (2%) |
| Agitation and confusion | 0 | 2 (1%) | 2 (1%) |
| Number of AEs | 123 | 167 | 290 |
| Number of patients experiencing an event | 76 | 105 | 181 |
| Total number of patients | 141 | 245 | 386 |
Procedure-related adverse events: observational
The maximum number of events reported for a single patient was five. Please see Appendix 10 for full table.