Our search yielded 12,182 results across three databases: PubMed (n = 3,832), Scopus (n = 4,750), and Web of Science (n = 3,600). Duplicates (n = 6,640) were removed after the search was completed. The remaining studies (n = 5,542) were screened based on their titles and abstracts, and studies not relevant to our systematic review were removed (n = 5,494). Major reasons for exclusion based on the title and abstract screening were classified as studies irrelevant to AC (n = 2,741), studies without pregnant patients (n = 903), animal studies (n = 864), literature reviews, book chapters, abstracts, and commentaries (n = 571), non-English (n = 270), commentaries and letters to editors (n = 145). If more than one reason was applicable for exclusion, only one criterion was recorded. The remaining articles (n = 48) were then fully read for eligibility criteria. Nine studies met the eligibility criteria based on the inclusion and exclusion criteria above and were included in the final review (Fig. 1).
The articles’ information is summarized in Supplementary Table 2. Of the nine studies included, five (55.6%) were from the USA [39–43], followed by Japan [44], Oman [45], Poland [46], and Pakistan [47], with one (11.1%) study each.
All studies reported one case. Overall, nine patients with ten fetuses (one twin pregnancy reported by Meng et al. [41]) were included (Table 1). Apart from one study (11.1%) which used AC for pseudoaneurysm [42], all other papers (88.9%) treated tumors via AC [39–41, 43–47]. The awake-awake-awake approach was the most common protocol used in seven studies (77.8%) [40–43, 45–47]. One study (11.1%) used the asleep-awake-asleep protocol [44], and another (11.1%) did not specify their protocol [39].
Table 1
Study | Study design | Single/multi center | Condition treated | Patients number | Fetus number | AC protocol | Primary sedation and analgesic |
Abd-Elsayed et al., 2013 | Retrospective | Single center | Tumor | 1 | 1 | NS | Anaesthesia induction and maintenance: propofol/alfetanil |
Handlogten et al., 2015 | Case study | Single center | Tumor | 1 | 1 | Awake-awake-awake | Local anesthesia: 0.25% bupivicance with 1:200,000 epinephrine. Sedation: initial infusion of 0.4 to 0.5 µg/kg/h of dexmedotomidine without a loading dose. Intermittent boluses of propofol at 10–30 mg or fentanyl 25µg administered as needed for stimulating events, such as urinary catheter placement. |
Meng et al., 2016 | Caee study | Single center | Tumor | 1 | 2 | Awake-awake-awake | Local anesthesia: 1:1 mixture of 0.5% lidocaine and 0.25% bupivacaine. Conscious sedation: propofol (25–60 mcg/kg/min) and remifentanil (0.04–0.14 mcg/kg/min) |
Hedayat et al., 2017 | Case study | Single center | Pseudoaneurysm | 1 | 1 | Awake-awake-awake | Fentanyl and diprovan (dose NS) |
Kamuta et al., 2017 | Case study | Single center | Tumor | 1 | 1 | Asleep-awake-asleep | Local anesthesia: 40 ml of 0.3% ropivacaine and 10 ml of 1% lidocaine with 0.01% epinephrine. Induction: fentanyl 125 µg and thiopental 375 mg. Maintenence: sevoflurane and remifentanil at 0.3 µg/kg/min. Conscious sedation: dexmedetomidine started at 1.0 ug/kg/hr and continued at 0.7 µg/kg/hr after 20 min. Surgical site closure: fentanyl 225 µg and droperidol 100 µg. |
Al Mashani, 2018 | Case study | Single center | Tumor | 1 | 1 | Awake-awake-awake | Local anesthesia: 0.25% bupivicaine and 1% lidocaine (1:1 mixture). Conscious sedation: low-dose propofol (50 mcg/kg/min), remifentanil (0.1 mcg/kg/min), and dexmedetomidine (0.5 mcg/kg/min). Propofol was stopped and dexmedetomidine was reduced before neurophysiologic testing (0.3 mcg/kg/min). |
Pawlik et al., 2018 | Case study | Single center | Tumor | 1 | 1 | Awake-awake-awake | Local anesthesia: 15ml of 1% ropivicaine and 15 ml of 1.0% lidocaine with 1:40000 epinephrine. Conscious sedation: dexmedetomidine at 0.4 to 0.7 mcg/kg/hr without a loading dose, and remifentanil of 1–2 ng/ml. Dexmedetomidine infusion was increased to 1.0 mcg/kg/hr and remifentanil to 3–4 ng/ml during mitigating events (such as scalp block infiltration, and head immobilization). |
Kumar et al., 2020 | Case study | Single center | Tumor | 1 | 1 | Awake-awake-awake | NS |
Gunasekaran et al., 2022 | Case study | Single center | Tumor | 1 | 1 | Awake-awake-awake | Local anesthesia: 2% lidocaine with 1:10000 epinephrine and 0.5% ropivicaine mixed 1:1. Conscious sedation: remifentanil, dexmedetomidine, and propofol. |
NS, not specified |
Medications
As the use of propofol in pregnant patients is prohibited, Kamata et al. [44] used sevoflurane and remifentanil for general anesthesia until the first scan of iMRI, and they subsequently re-induced dexmedetomidine when tumor removal had been accomplished. Also, they used prophylactic antiemetics and antacids to prevent intraoperative vomiting. Similarly, Hedayat and colleagues [42] used dexamethasone and ondansetron to provide antiemetic effects. Furthermore, they used ranitidine and oral sodium citrate to decrease the acidity of gastric contents to avoid aspiration.
The mean age of patients was 29.8 ± 4.5 years old, with the youngest patient being 24 [43], and the oldest, 40 [39] (Table 2). One study (11.1%) did not specify the patient's age [42]. Astrocytoma was the most common pathology reported in three (33.3%) patients. Glioma was the most represented pathology in six (66.7%) patients [39–41, 43, 44, 46]. Pseudoaneurysm [42], and meningioma [47] were reported in one study (11.1%) each. One study (11.1%) did not specify the pathology [45]. The shortest operation time was two hours [43], whereas the longest procedure took 8 hours and 29 minutes to complete [40]. Four studies (44.4%) did not report their operation time [39, 41, 42, 45]. Lateral/semi-lateral was the common surgical position in four (44.4%) studies [41, 43, 45, 46]. The supine position was employed in two (22.2%) studies [40, 44], and three (33.3%) studies did not specify their surgical position [39, 42, 47].
Table 2
Study | Age (year) | Weight and height | Pathology | Presentation | Past medical history | AC operation time (range) | Surgical position | Follow-up |
Abd-Elsayed et al., 2013 | 40 | NS | Glioma | Seizure | NS | NS | NS | NS |
Handlogten et al., 2015 | 27 | 70 Kg, 172 cm | Anaplastic oligoastrocytoma (WHO grade III) | New onset seizure, mild receptive and expressive aphasia | NS | 8 hours and 29 minutes | Supine with left uterine displacement | 30 months |
Meng et al., 2016 | 31 | NS | Anaplastic astrocytoma (WHO grade III). | Word finding difficulty, dysfluency, right upper extremity plegia, and right lower extremity pariesis. | Two general anesthesia tumor debulking during the same pregnancy at 16 weeks and 28 weeks gestation | NS | Right semilateral | NS |
Hedayat et al., 2017 | NS | NS | 5mm cortical pseudoaneurysm of the distal right middle cerebral artery under previous craniotomy site | Intermittent headaches, dizziness, and tingling of hands | Previous craniotomy due to superficially penetrating gunshot wound with complete neurological recovery | NS | NS | NS |
Kamuta et al., 2017 | 30 | 61.4 Kg, 162 cm | Anaplastic astrocytoma (WHO grade III). | Generalized convulsive seizures that were poorly controlled with anti-convulsive therapy | NS | 241 min (surgery), 291 min (anesthesia) | Supine with a wedge placed under the right buttock to prevent aortocaval compression. | 17 months |
Al Mashani, 2018 | 26 | NS | NS | Recurrent seizures for one week | NS | NS | Left lateral position | NS |
Pawlik et al., 2018 | 31 | NS | Astrocytoma (Grade II/III) | Word finding difficulty | NS | 4 hours and 40 minutes. | Semi-lateral | NS |
Kumar et al., 2020 | 29 | 53 Kg, 153 cm | Meningioma | Left eye blurred vision | Non-significant | 4 hours. | NS | 1 week- Complete resolution of symptoms |
Gunasekaran et al., 2022 | 24 | NS | Giant cell glioblastoma WHO grade IV | Generalized tonic-clonic seizure, frequent headaches, right leg numbness and weakness, difficulty with memory and cognition. | Systematic lupus erythematous (1, 100%) | 2 hours | Left lateral decubitus | 1 year- Brain MRI showed no further pathology |
WHO, World Health Organization |
Six (66.7%) lesions were in the left hemisphere [39–41, 43, 44, 46], whereas the other three (33.3%) were in the right hemisphere [42, 45, 47] (Table 3). The frontal lobe was the most common pathology region reported in four studies (44.4%) [39, 43, 44, 47], followed by frontoparietal regions in two (22.2%) [41, 45]. Temporal [40] and parietal [46] lobes pathologies were each reported in one study (11.1%). One (11.1%) study did not specify the pathologic lobe [42]. All studies employed intraoperative fetal monitoring, and seven studies (77.8%) specified fetal heart rate monitoring [39–45]. Two (22.2%) studies did not specify their type of monitoring [46, 47].
Table 3
Study | Lesion hemisphere | Lesion location | Eloquent area lesion and mapping (n, %) | Intraoperative fetal monitoring | Preoperative localization | AC extent of resection (n, %) |
Abd-Elsayed et al., 2013 | Left (1, 100%) | Frontal lobe (1, 100%) | NS | Yes- Heart rate | NS (2.4 × 2.2 cm) | NS |
Handlogten et al., 2015 | Left (1, 100%) | Temporal lobe (1, 100%) | Motor and speech (1, 100%) | Yes- Heart rate and movement | MRI (4.5 × 3.2 × 3.5 cm intracranial mass) | Total/near total |
Meng et al., 2016 | Left (1, 100%) | Frontoparietal white matter (1, 100%) | Language and sensorimotor (1, 100%) | Yes- Heart rate and contraction | MRI (7 × 6 × 5 cm anterior– posterior transverse cranio–caudal) | Subtotal (1, 100%)- Residual disease at the perironlandic region, deep parietal grey matter, and deep frontal regions |
Hedayat et al., 2017 | Right (1, 100%) | NS | NS | Yes- Heart rate | CT and cerebral angiography | NS |
Kamuta et al., 2017 | Left (1, 100%) | Frontal lobe (1, 100%) | Motor (1, 100%) | Yes- Heart rate | MRI (6 cm) | Total/near total |
Al Mashani, 2018 | Right (1, 100%) | Frontoparietal region (1, 100%) | Motor and speech (1, 100%) | Yes- Tococardiography | MRI (8.2 × 4.5 × 4.6 cm) | NS |
Pawlik et al., 2018 | Left (1, 100%) | Parietal lobe (1, 100%) | Speech (1, 100%) | Yes- NS | MRI (NS) | NS |
Kumar et al., 2020 | Right (1, 100%) | Frontal lobe (1, 100%) | Motor (1, 100%) | Yes- NS | MRI (extra-axial- NS) | Total (1, 100%) |
Gunasekaran et al., 2022 | Left (1, 100%) | Frontal lobe (1, 100%) | Motor (1, 100%) | Yes- Heart rate using Doppler | MRI (2.0 × 1.5 × 1.5 cm intracranial mass at the level of the coronal suture) | Total (1, 100%) |
CT, comouterized tomography; MRI, magnetic resonance imaging; NS, not specified |
Pre-, Intra-, And Post-operative Monitoring Of The Fetus
On the day of the AC, Gunasekaran et al. [43] used Doppler to assess the fetal cardiac activity which was indicated as normal. Post-operative Doppler examination also redemonstrated normal fetal activity once the patient was transported to the recovery room. In another study by Kumar and colleagues [47], the fetal heart sounds were monitored pre-operatively by an obstetrician, who administered cyclogest 800 mg rectally as a tocolytic agent.
The mean gestational age at diagnosis was 13.6 ± 6.5 weeks (Table 4). The earliest diagnosis was at two weeks [42], and the latest was at 22 weeks [46] pregnancy. One study (11.1%) did not specify the gestational age at diagnosis [41]. The mean gestational age at craniotomy was 19.6 ± 6.9 weeks with the earliest AC reported on week nine [43], and the latest one at the 30th week [41]. In total, 10 healthy babies were delivered from patients who underwent AC.
Table 4
Study | Gestational age at diagnosis (week) | Gestational age at craniotomy (week) | Pregnancy term | Delivery method | Hospitalization length | AC intraoperative complications (n, %) | Neonatal outcome |
Abd-Elsayed et al., 2013 | 18 | 22 | No | NS | NS | None | Viable infant with normal Apgar score |
Handlogten et al., 2015 | 16 | 20 | Yes | Vaginal | NS | None | Healthy baby delivered vaginally at term. |
Meng et al., 2016 | NS | 30 | No- 31 weeks | Under spinal anaesthesia on post-operative day 4 | NS | NS | Two babies were uneventfully delivered. |
Hedayat et al., 2017 | 2 | 23 | Yes | NS | NS | Unsuccessful primary reconstruction of vessel and aneurysmorrhaphy. Attempted end-to-end bypass was also unsuccessful. | The fetus was delivered at term with no obstetric or neurological complications. Pre-, intra-, and post-operative monitoring of the fetus's heart rate showed no abnormalities or variabilities. |
Kamuta et al., 2017 | 21 | 27 | No- 35 weeks and 2 days | NS | NS | No complications | Healthy baby of 2137g delivered at 35 weeks and 2 days gestation. The baby did not show any evidence of medical or developmental concern at 17 months follow-up. |
Al Mashani, 2018 | 10 | 10 | NS | NS | NS | None | NS regarding delivery, did mention that post-op the fetal status was satisfactory. |
Pawlik et al., 2018 | 22 | 22 | NS | NS | NS | None | No changes in fetal status post-op were observed. No foetus or intrauterine volume abnormalities were discovered in ultrasound a day following AC. |
Kumar et al., 2020 | 13 | 13 | NS | NS | 3 days | NS | No changes in fetal status post-op. Viable heart sounds were heard post-op indicating the fetus viability. |
Gunasekaran et al., 2022 | 7 | 9 | No- the baby was delivered at 34 weeks gestation | Cesarean section | 1 day | None | No change in fetal status post-op was observed. Doppler monitoring was completed and demonstrated a normal fetal heart rate. The baby was born via cesarian section at 34 weeks gestation due to preterm premature rupture of membranes and concerning fetal monitoring findings (NS). The baby was 5 months old and healthy when the article was written. |
NS, not specified |
None of the AC procedures was converted to general anesthesia. A summary of outcomes from each study is summarized in Table 5.
Table 5
Study | Conversion to GA (n, %) | Preoperative neurological symptoms (specify/ n, %) | Postoperative complications (n, %) | Postoperative neurological deficits resolved | Main outcome |
Abd-Elsayed et al., 2013 | No | N/S | Patient deceased 16 months after craniotomy | NS | AC caused no intra-, or post-op complications. The baby was delivered with normal apgar scores. The patient deceased 16 months after the craniotomy. |
Handlogten et al., 2015 | No | Seizure, expressive & receptive aphasia | No new neurological deficits | NS | Use of dexmedetomidine and mannitol during awake craniotomy in a single pregnant patient did not lead to notable maternal and fetal adverse effects. There were no intra-op or post-op complications and no newly developed post-op neurologcal deficits. Use of mannitol did lead to a transient 30% reducrtion in internal uterine volume but had no overt maternal or fetal/neonatal adverse effects. A healthy baby was delivered uneventfully at term. |
Meng et al., 2016 | No | Dysfluency, word-finding difficulty, right upper extremity paralysis, right lower extremities weakness | No immediate post-op deficits. Receiving hospice care 12 months post-AC. Walking impairment due to progressive worsening of right leg weakness caused Comprehensible but slurred speech. | Significant improvement in fluency with naming and speech comprehension POD1, but with impaired repetition. Strength of right arm and leg returned to baseline except for a weak handgrip. | Study examined awake craniotomy for removal of tumor in a 30 week pregnant patient with twins, who had underegone two previous craniotomies under GA at 16 and 28 week gestation. The patient showed significant POD1 improvement in naming and comprehension, and strength of right arm and leg returned to baseline apart from weak hand grip. No intra-op complications were seen. Babies were delivered uneventfully on POD4 under spinal anesthesia. 12 months post-op patient is receiving hospice care, with progressive worsening of right leg weakness and slurred speech. |
Hedayat et al., 2017 | No | Intermittent headaches, diziness, and hand tingling | No post-op neuroloigcal deficits | NS | AC for management of a pseudoaneurysm in a pregnant female at 23 week gestation was successfully done without any post-operative neurological complications. Pre and post-operative fetal heart rate monitoring showed no variabilities or abnormalities. The baby was successfully delivered at term. No neurological complications were observed in follow-up visits. |
Kamuta et al., 2017 | No | Generalized convulsive seizures | None | NS | AC, via the asleep-awake-asleep protocol, for removal of high grade glioma in a pregnant patient at 27 week gestation was successfully conducted with full tumor resection. No intra-operative or post-operative complications were seen. The patient delivered a healthy baby at 35 weeks gestation. At the 17 month follow-up, there was no evidence of tumor recurrence in the patient and no developmental or medical concerns for the child. |
Al Mashani, 2018 | No | Seizures- unspecified what type | None | NS | AC for tumor removal in a pregnant patient at 10 week gestation was successfully completed with no intra-operative or post-operative complications. The fetal status was satisfactory intra-operatively and post-operatively, there was no information provided regarding the pregnancy. |
Pawlik et al., 2018 | No | Speech finding difficulty | NS | NS | AC for tumor removal in a pregnant patient at 22 week gestation was successfully completed with no intra-operative complications. Obstetric abdominal ultrasound was done before, immediately after, and the next day after surgery and all showed no fetal or intrauterine volume abnormalities. AC has neuroprotective effects for the patient and is feasible during pregnancy. |
Kumar et al., 2020 | No | Left eye blurred vision | NS | Yes- complete resolution of symptoms post-op | AC for tumor removal in a pregnant patient at 13 week gestation was successfully completed with complete resolution of symptoms at one-week follow-up. Extensive pre-op psychological preparation was done as part of anesthetic management. Post-op obstetric review showed fetus viability as evident by fetal heart rate sounds. AC facilitates intraoperative neurological monitoring, provides hemodynamic stability with improved fetal-maternal outcomes. |
Gunasekaran et al., 2022 | No | Generalized convulsive seizures, subjective right leg numbness and weakness, and difficulty with concentration and memory | NS | NS | AC for glioblastoma resection in a 24 year old patient who was pregnant in her first trimester was successfully completed with gross total resection of tumor. There were no intra-operative complications and after interdisciplinary care with adjuvant radiotherapy, one year follow-up showed no further disease. There were no post-op fetal complications and a healthy baby was born at 34 weeks gestation. At the time the article was written, the baby is 5 months old and in good health. AC is a safe and effective process for resection of glioblastoma in pregnancy. |