Emergence is defined as the transition from the sleep state to full consciousness [1]. Emergence from general anesthesia is usually smooth and uneventful. Inadequate emergence is characterized by a disturbance of activity level in the immediate postoperative period and is classified into two subtypes—emergence agitation and hypoactive emergence. Emergence agitation may consist of hallucinations, delusions, and confusion that manifests as restlessness, moaning, involuntary physical activity, and thrashing [2], while a delayed recovery characterizes hypoactive emergence after anesthesia. However, there are no clear diagnostic criteria defining emergence agitation or hypoactive emergence [3]. The term ‘emergence delirium’ is often misused in the literature as a reference to emergence agitation, whereas agitation and delirium have distinctive descriptions in the Diagnostic and Statistical Manual of Mental Disorders (DSM) Fifth Edition [4]. Problems of post-anesthesia emergence have been shown to occur in 5–10% of general surgery patients of all ages. Its incidence is even higher after the preoperative use of benzodiazepines, breast surgery, abdominal surgery, musculoskeletal surgery, long operation durations, induction of anesthesia with etomidate, a pain numeric rating scale (NRS) of 6 to 10 in the post-anesthesia care unit (PACU), as well as at both extremes of patient age [5–7]. The clinical importance of inadequate emergence in either form has not been thoroughly investigated. It is shown that patients with emergence agitation are at an increased risk of injury, hemorrhage, extended PACU stay, morbidity, mortality, and resource utilization [5,8,9]. However, hypoactive emergence has rarely been studied. Radtke et al. [6] found 60 of 1,868 patients presented hypoactive emergence in their study (3.2%), which was more common for younger age, longer duration of surgery, and intra-abdominal surgery.

This prospective observational study aimed to define the incidence and risk factors of inadequate emergence (both emergence agitation and hypoactive emergence) that was resolved by the time of PACU discharge in adult patients after general anesthesia for elective surgery. It was shown earlier that psychological problems such as depression and anxiety, as well as alterations in organ functions, were significantly higher in substance-dependent patients [10,11]. Furthermore, clinical findings indicate that baseline psychological disorders such as anxiety and depression can be associated with postoperative delirium emergence [12]. Moreover, due to the progressively high frequency of substance dependence in the general population [13,14], we focused our study on substance dependence and its relationship with inadequate emergence.

This research was done per the Principles for Medical Research Involving Human Subjects, outlined in the Helsinki Declaration of 1975 (revised 2018). After institutional ethics committee approval with IRB number 86100059 , patients classified with an American Society of Anesthesiologists I–III physical status and undergoing elective general anesthesia during the six months period from March to September 2018 were enrolled in this prospective observational study with their informed consent. The study excluded patients under 18 years old, with a history of dementia, cerebral insult, intracranial surgery, or those under neuraxial and regional anesthesia. Anesthesia was induced according to standard protocols in our department—(1) preoxygenation and intravenous induction using a short-acting narcotic, ketamine, sodium thiopental, or propofol and neuromuscular blockade using succinylcholine or atracurium, (2) maintenance of anesthesia using volatile anesthetics or total intravenous anesthesia, short-acting or long-acting narcotics, and ketamine, (3) reversal of neuromuscular blockade using neostigmine and atropine, and (4) awake extubation and transportation to the PACU. In the PACU, all patients received oxygen if their oxygen saturation was below 95% in room air. Postoperative pain management included optional non-opioid analgesics for mild postoperative pain (NRS 3–4) or opioid analgesics for moderate to severe pain (NRS ≥ 5). Patients were assessed at 10 minutes after admission to the PACU by experienced anesthesia nurses who were blinded to the patient care. The NRS pain score was recorded, and the presence of inadequate emergence and its severity was determined according to the Richmond Agitation-Sedation Scale (RASS, Table 1). Emergence agitation was defined as RASS ≥ +1, normal emergence was defined as RASS between 0 and –1, and hypoactive emergence was defined as RASS ≤ –2 [6].

The following variables for each patient were recorded—age, gender, body mass index; pre-existing medical conditions, psychological disorders, history of substance dependency (alcohol, opium, stimulants, psychedelics; according to DSM IV criteria), type of surgery, smoking, intraoperative estimated blood loss, intravenous fluid administration, transfusion, type and dosage of intraoperative analgesics, having a urinary catheter in the PACU, type and dosage of postoperative analgesics, and postoperative pain score (NRS).

In this study, 1,136 patients were enrolled, including 770 female patients (68%). The mean age was 39 years (range 18–99 yr). Inadequate emergence in the PACU occurred in 231 patients (20.3%), out of which, 158 patients (13.9%) had emergence agitation, and 73 patients (6.4%) had hypoactive emergence. Substance dependence was reported in 95 patients (8%) of whom, 62.1% abused opium, and 37.9% abused stimulants. All patients regained a normal cognitive status before discharge from the PACU. The mean ± SD of stay time in PACU was 47 ± 13 minutes, which was not significantly different in subgroups comparison: substance-dependent vs. normal patients (P = 0.654) as well as patients with vs. without inadequate emergence (P = 0.321).

Inadequate emergence in adult patients has rarely been examined. Thus, there are only a few recommendations regarding treatment, except for pediatric anesthesia. Caution is warranted for patients at increased risk. Based on pediatric anesthesia, it may be helpful to keep patients away from stressful stimuli by providing a quiet, darkened recovery room. If necessary, it is appropriate to administer additional analgesics and a sedative [15]. IV propofol (0.5 mg/kg) or IV midazolam (0.02 mg/kg) have both been used successfully in treating emergence agitation in children [16,17]. One in every five patients in our study experienced inadequate emergence. It is a significant issue that deserves more attention [5,6,18]. Despite the scarcity of studies with reports on hypoactive emergence [6], emergence agitation has been evaluated more extensively. In children, emergence agitation is frequently a complication, with described incidences up to 60% [19,20]. However, the incidence of emergence agitation in adults has been about 5% in most studies [5,6], which is lower than our observation. There are different scales of agitation assessment, such as the Richmond Agitation-Sedation Scale (RASS), Riker Sedation-Agitation Scale (SAS), Motor Activity Assessment Scale, and the New Sheffield Sedation Scale. They are more precise in the evaluation of agitation than the Ramsay sedation scale, which rates sedation. Studies have demonstrated that both RASS and SAS have excellent inter-rater reliability [21–23]. These scales have been used for adults in intensive care units and are not well-established in the PACU. However, these scales are useful, especially in emergencies.