Table 2.
Primate studies of anaesthetic-induced neuroapoptosis. PND, post-natal day; GA, gestational age; MAC, mean alveolar concentration
| Reference | Species | Age | Anaesthetic | Duration (h) | Histology outcome | Neurodevelopmental outcome |
|---|---|---|---|---|---|---|
| Slikker and colleagues, Toxicol Sci 2007; 98: 145–58 | Rhesus macaques (Macaca mulatta) | GA 122 days or PND 5 or PND 35 | Ketamine 20 mg kg−1 i.m. followed by infusion of 20–50 mg kg−1 h−1 i.v. to maintain light surgical plane of anaesthesia | 3 or 24 h | Increased apoptosis, necrosis, and NMDA-receptor NR1 subunit expression in neonatal brains after 24 h ketamine at GA 122 or PND 5 but not PND 35 or with shorter duration ketamine | N/A |
| Zou and colleagues, Int J Dev Neurosci 2009; 27: 727–31 | Rhesus macaques (Macaca mulatta) | PND 5–6 | Ketamine 20 mg kg−1 i.m. followed by infusion 20–50 mg kg−1 h−1 i.v. to maintain light surgical plane of anaesthesia | 3, 9, or 24 h | Time-dependent increased apoptosis and necrosis seen after ketamine 9 or 24 h, not seen at 3 h. Apoptosis prominent in neocortical areas, especially frontal cortex | N/A |
| Brambink and colleagues, Anesthesiology 2010; 112: 834–41 | Rhesus macaques | PND 5–6 | Isoflurane, end-tidal 0.7–1.5 vol% to maintain light surgical plane of anaesthesia | 5 h | Increased apoptosis. Temporal and somatosensory cortices most severely affected | N/A |
| Zou and colleagues, Neurotox Teratol 2011; 33: 592–7 | Rhesus macaques | PND 5–6 | N2O 70%, isoflurane 1% alone or combination | 8 h | Increased apoptosis with combination anaesthesia but not with N2O or isoflurane alone. Frontal and temporal cortices and hippocampus most severely affected | N/A |
| Paule and colleagues, Neurotoxicol Teratol 2011; 33: 220–30 | Rhesus macaques | PND 5–6 | Ketamine 20 mg kg−1 i.m. followed by infusion 20–50 mg kg−1 h−1 i.v. to maintain light surgical plane of anaesthesia | 24 h | N/A | At 7 months and persistent at 3.5 yr, the ketamine group had poorer performance in learning, colour, and position discrimination tasks; slower response speed; lower motivation |
| Brambink and colleagues, Anesthesiology 2012; 116: 372–84 | Rhesus macaques | GA 120 days or PND 6 | Ketamine i.v. 10–20 mg kg−1 bolus then 10–85 mg−1 kg−1 h−1 infusion to maintain intermediate surgical plane of anaesthesia | 5 h | Widespread apoptosis in all groups. Loss of neurones 2.2× greater in fetuses than in neonates. Damage throughout fetal brain; damage maximal in basal ganglia in neonatal brain | N/A |
| Brambink and colleagues, Ann Neurol 2012; 72: 525–35 | Rhesus macaques | PND 6 | Isoflurane, end-tidal 0.7–1.5 vol% to maintain light surgical plane of anaesthesia | 5 h | Significant apoptosis seen throughout CNS in both white and grey matter. Fifty-two per cent dying cells were glia, 48% were neurones. Oligodendrocytes engaged in myelinogenesis were selectively vulnerable | N/A |