Table 1.

Anaesthetic technique and strategy in management of inadequate analgesia

Study	Anaesthetic technique	Titrating strategies
Ahmad 2003	Endotracheal GA. Induction: sevoflurane Maintenance: sevoflurane‐sufentanil‐nitrous oxide‐a relaxant	Sevoflurane/sufentanil titrated for increased blood pressure/heart rate > 20%, despite a BIS value of 50‐60 or end tidal sevoflurane concentration 2%
Aime 2006	Endotracheal GA, Induction: propofol‐sufentanil Intubation: atracurium Maintenance: sevoflurane and nitrous oxide in oxygen, sufentanil, atracurium	BIS group: intermittent bolus dose of sufentanil despite BIS or Entropy values within the recommended range Control group (CS group): increased sevoflurane concentration or intermittent bolus doses of intravenous sufentanil for signs of inadequate anaesthesia, i.e. hypertension and bradycardia
Anez 2001	LMA GA. Induction: propofol‐alfentanil Maintenance: propofol‐rocuronium	NA
Assare 2002	LMA GA. Induction: propofol‐fentanyl Lidocaine infiltration prior to incision Maintenance: sevoflurane‐nitrous oxide (no muscle relaxant)	NA
Basar 2003	Endotracheal GA. Induction: fentanyl‐thiopentone Intubation: rocuronium Maintenance: sevoflurane‐nitrous oxide	Inadequate analgesia in both groups managed by increased concentration of sevoflurane (no supplemental fentanyl)
Boztug 2006	Endotracheal GA. Induction: fentanyl‐thiopentone Intubation: cis‐atracurium Maintenance: 50% O2/air mixture and 0.8%–1.5% sevoflurane, fentanyl, and cis‐atracurium	BIS group: additional fentanyl was administered in 0.1mg doses when the BIS value rose to 55. With inadequate decreases in the haemodynamic values, sevoflurane concentration was increased by 20% Control (CS) group: fentanyl was also administered in 0.1‐mg doses if MAP increased by 20% from baseline values, and in the event of inadequate decreases in the haemodynamic values, the sevoflurane concentration was increased by 20%
Bruhn 2005	Endotracheal GA. Induction: remifentanil‐propofol Intubation: cis‐atracurium Maintenance: desflurane in O2/air mixture and remifentanil (no more neuromuscular blocking agents)	BIS group: desflurane during maintenance was continuously adjusted according to a target value of ‘50’. In case anaesthesia was judged inadequate despite the BIS target value, the infusion rate of remifentanil could be increased. Control (CS) group: if anaesthesia was inadequate, the desflurane concentration was increased in steps of 0.5 vol%. If this was judged insufficient, the infusion rate of remifentanil could be increased
Chiu 2007	Endotracheal GA. Induction: fentanyl‐propofol Intubation:rocuronium Maintenance: before cardiopulmonary bypass ‐sevoflurane (end tidal concentration 0.5‐1.5%) with oxygen in air + infusion atracurium: during cardiopulmonary bypass ‐propofol starting TCI from 2 µG/ml in both arms	BIS group: adjustment of the propofol infusion to achieve BIS 40 to 50 Control (CS) group: titrating of TCI propofol according to perfusion pressure (70 to 90 mmHg)
Ellerkmann 2010	Endotracheal GA plus regional anaesthesia for intraoperative and postoperative pain control Induction: remifentanil, propofol Intubation:cis‐atracurium Maintenance: propofol infusion, remifentanil infusion	During maintenance of anaesthesia, all patients were assessed for signs of inadequate anaesthesia, hypotension or bradycardia. Inadequate anaesthesia was defined as hypertension, tachycardia or patient movement, eye‐opening, swallowing, grimacing, lacrimation or sweating. The definition of adverse haemodynamic responses was adapted from Garrioch et al15: responses were classified as ‘hypertension’ (SAP >40 mmHg from baseline), ‘hypotension’ (SAP <40 mmHg from baseline), ‘tachycardia’ (HR >100 beats/minute‐1) and ‘bradycardia’ (HR <45 beats/minute‐1). In the standard practice group, if anaesthesia was judged inadequate the propofol concentration was increased in steps of 1 mg/kg/hour as necessary
Gan 1997	Endotracheal/LMA anaesthesia Induction: propofol alfentanil Maintenance: 50%nitrous in oxygen‐propofol‐alfentanil‐relaxants	BIS group: increasing alfentanil if BIS was within the recommended range (45‐60) SP group: increasing doses of either propofol, alfentanil or antihypertensive agents
Hachero 2001	Endotracheal GA. Induction: propofol Intubation: mivacurium Maintenance: propofol‐fentanyl‐mivacurium	Signs of inadequate anaesthesia managed in both groups by fentanyl
Ibraheim 2008	Endotracheal GA. Induction: fentanyl‐propofol Intubation: succinylcholine. Maintenance: sevoflurane, nitrous oxide in oxygen, fentanyl, and atracurium	Any instances of inadequate anaesthesia were managed by increasing the concentration of sevoflurane
Kamal 2009	Endotracheal GA. Induction : propofol, Intubation:atracurium Maintenance: sevoflurane, 50% nitrous oxide in oxygen, atracurium by TOF, fentanyl	BIS group:If the patient in that group, exhibited hypertension or tachycardia the mode of treatment was dependent on the BIS index. If the BIS index was >60, anaesthesia was deepened by increasing sevoflurane concentration until BIS index was between 50 and 60. If BIS index was already in the targeted range and the patient exhibited hypertension or tachycardia, fentanyl 25‐50 μg IV was given. If BIS index was <50, sevoflurane was decreased and patient was checked for signs of lack of analgesia (i.e., lacrimation, grimacing, movement). In case of lack of analgesia, fentanyl 25‐50 μg IV was administered. But if no signs of lack of analgesia, labetalol 5‐10 mg IV was administered Standard practice group: If the patient in this group exhibited hypertension (mean arterial blood pressure >25% above baseline) (MBP) and tachycardia (heart rate (HR) >90 beats min‐1), anaesthesia was deepened either by increasing inspired sevoflurane concentration, or administering fentanyl 25‐50 μg or labetalol 5‐10 mg IV. The mode of treatment was left to anaesthesiologist’s discretion
Kreuer 2003	Endotracheal GA. Induction: propofol‐remifentanil Intubation: cisatracurium. Maintenance: propofol (TCI)‐ remifentanil (constant infusion)	Remifentanil infusion was given in both groups for signs of inadequate anaesthesia despite achieving propofol target concentration or a target value of 50 for BIS
Kreuer 2005	Endotracheal GA, Induction: propofol‐remifentanil Intubation: cis‐atracurium Maintenance: desflurane in O2/air mixture and remifentanil ( no more neuromuscular blocking agents)	BIS group: desflurane during maintenance was continuously adjusted according to a target value of ‘50’. In case anaesthesia was judged inadequate despite the BIS target value, the infusion rate of remifentanil could be increased. Control (CS) group: if anaesthesia was inadequate, the desflurane concentration was increased in steps of 0.5 vol%. If this was judged insufficient, the infusion rate of remifentanil could be increased
Leslie 2005a	Relaxant general anaesthesia. Induction: midazolam‐propofol or thiopentone Intubation: nondepolarizing muscle relaxants. Maintenance: propofol or volatiles‐nitrous oxide‐opioids. Hypnotic drugs. Combined general and regional anaesthesia	Narcotic analgesics on the discretion of the attending anaesthesiologists
Luginbuhl 2003	Endotracheal GA Induction: propofol and fentanyl. Intubation: vecuronium Maintenance: propofol‐fentanyl or desflurane‐fentanyl	BIS group: propofol or desflurane to keep BIS 45‐55 and opioids according clinical criteria CS group: propofol or desflurane and opioids according to haemodynamic and vital sign criteria (within 20% of the baseline value)
Masuda 2002	Endotracheal GA Induction: propofol‐fentanyl Intubation: vecuronium Maintenance: propofol‐nitrous oxide ‐ fentanyl‐vecuronium	NA
Morimoto 2002	Endotracheal GA Induction:thiopentone, Intubation: vecuronium Maintenance: sevoflurane‐nitrous oxide‐ fentanyl‐vecuronium	Managed by fentanyl 50‐100 µg, despite 2% in sevoflurane in both groups
Myles 2004	Relaxant general anaesthesia. Induction: midazolam‐propofol or thiopentone Intubation: nondepolarizing muscle relaxants. Maintenance: Propofol or volatiles‐nitrous oxide‐opioids. Hypnotic drugs. Combined general and regional anaesthesia	Narcotic analgesics on the discretion of the attending anaesthesiologists
Nelskyla 2001	Endotracheal GA. Induction:propofol Intubation: rocuronium Maintenance: Sevoflurane (0.94%‐1.4%)‐nitrous oxide‐rocuronium	Supplemental alfentanil given for haemodynamic variables >25% of the preanaesthetic value, despite BIS of 50‐60 in BIS group or sevoflurane concentration of 1.4% in CP group
Paventi 2001	Endotracheal GA. Induction: remifentanil ‐ thiopentone Intubation: vecuronium Maintenance: sevoflurane‐nitrous oxide‐remifentanil‐vecuronium	Remifentanil infusion (0.4 µG/kg/min) for both groups
Puri 2003	Endotracheal GA. Induction: midazolam‐morphine‐thiopentone Intubation:vecuronium. Maintenance: isoflurane‐nitrous oxide‐morphine	Signs of inadequate analgesia (tachycardia, hypertension, sweating, lacrimation etc) in both groups managed by morphine before vasodilators or beta‐blocker
Recart 2003	Endotracheal GA Premedication: Induction: propofol‐fentanyl Intubation: rocuronium Maintenance: desflurane‐fentanyl	Intermittent intravenous fentanyl 0.5 mg/kg as needed to maintain haemodynamic variables within 15% of the baseline value Labetalol to control sympathetic responses as needed (in the presence of adequate hypnotic and analgesic states) Intermittent intravenous fentanyl 0.5 mg/kg as needed to maintain haemodynamic variables within 15% of the baseline value Labetalol to control sympathetic responses as needed (in the presence of adequate hypnotic and analgesic states)
Song 1997	Endotracheal GA. Induction: fentanyl‐propofol. Intubation:succinylcholine Maintenance: desflurane or sevoflurane‐nitrous‐fentanyl‐mivacurium (at least 1‐2 TOF)	Inadequate analgesia (haemodynamic variables >20%of baseline) managed by supplemental doses of fentanyl (25‐30 µg)
Struys 2001	Endotracheal GA. Induction: remifentanil, propofol .Intubation: rocuronium. Maintenance: remifentanil infusion (0.5 µg/kg/min)‐propofol infusion	Remifentanil infusion
Tufano 2000	Endotracheal GA. Induction: Propofol. Intubation: Cis‐atracurium. Maintenance: propofol infusion or sevoflurane‐nitrous oxide‐cisatracurium‐fentanyl	NA
White 2004	Endotracheal GA. Induction: propofol and fentanyl Intubation: succinylcholine. Maintenance: desflurane‐nitrous‐cisatracurium	Esmolol to treat sustained increased heart rate
Wong 2002	Endotracheal GA. Induction: propofol‐fentanyl‐midazolam Intubation: rocuronium. Maintenance: isoflurane‐nitrous oxide‐fentanyl‐rocuronium‐fentanyl	BIS group: BIS > 60 increasing isoflurane concentration; BIS = 50‐60 giving supplemental fentanyl; BIS < 50 decreasing isoflurane concentration and supplementing fentanyl (signs of inadequate anaesthesia) or labetalol (no sign of inadequate anaesthesia) Control(CS) group: increasing isoflurane concentration or supplemental fentanyl or labetalol for management of hypertension (>25%) or tachycardia (>90 beats per minute)
Zohar 2006	LMA GA. Induction: propofol‐fentanyl Maintenance: sevoflurane‐nitrous oxide (no muscle relaxant)	In both groups, the sevoflurane concentration was increased in response to signs of an inadequate “depth of anaesthesia” (e.g. movement in response to surgical stimulation)

GA = general anaesthesia, LMA = laryngeal mask airway, TCI = target controlled infusion

NA = not available