Preoperative anxiety is generally described as a state of discomfort or tension caused by disease, the ward environment, or worries about anesthesia and surgery before the operation; this state is often accompanied by somatic manifestations such as palpitations, dyspnea, sweating, frequent urination, abdominal pain, diarrhea or sleep disturbance [1]. The overall prevalence of preoperative anxiety varies widely from 11% to 80% in adult patients and is higher in women than in men [2, 3]. The incidence in children ranges from 41.7% to 75.44%, and the incidence in children aged 2 to 7 in China is similar to that in other countries, i.e., approximately 67.6% [4, 5]. Currently, the evaluation of preoperative anxiety still relies on multiple psychometric scales mainly including the State Trait Anxiety Inventory-State/Trait (STAI-S/T), the Amsterdam Preoperative Anxiety and Information Scale (APAIS), the Visual Analogue Scale for Anxiety (VAS-A), the Hospital Anxiety and Depression Scale-Anxiety (HADS-A), Generalized Anxiety Disorder 7 (GAD-7) and the modified Yale Preoperative Anxiety Scale (m-YAPS) [6, 7]. Nevertheless, there is no gold standard for assessing preoperative anxiety and multiple factors should be taken into consideration when choosing suitable scales such as their reliability and accuracy, the aim of the assessment, the patient’s age and clinical state and the type of surgery being planned [6].

Although postoperative adverse events are not yet well defined, their core essence includes medical practice-related events that can cause unnecessary or unpredictable hazards to patients or have the potential to produce harm, thus further increasing hospital costs, prolonging the time of hospitalization and affecting long-term prognosis [8, 9]. Excessive preoperative anxiety not only leads to sympathetic nervous excitement, causes cardiac oxygen consumption, and promotes platelet activation and aggregation, but also increases the occurrence of postoperative adverse events, such as hemodynamic instability, the usage of anesthetics, insomnia, pain, nausea and vomiting, neurocognitive dysfunction and even long-term mortality [10, 11].

Hence, in this narrative review we focus on the relationship between preoperative anxiety and postoperative adverse events, describe effective intervention strategies for preoperative anxiety and provide a summary and outlook.

1 Methodology

We searched online for papers that examined the relationship between preoperative anxiety and postoperative adverse events. We searched the PubMed, Scopus, Web of Science and Google Scholar databases from inception to 2022 using the following terms: ‘preoperative anxiety’, ‘postoperative adverse events’, ‘postoperative insomnia’, ‘postoperative sleep disturbance’, ‘postoperative pain’, ‘postoperative nausea and vomiting’, ‘perioperative neurocognitive disorders’, ‘postoperative cognitive dysfunction’ and ‘postoperative delirium’. We focused on the most recent and most relevant clinical studies. Basic research and articles that provided no abstract were excluded.

2 Preoperative anxiety and postoperative insomnia

Insomnia is a common sleep problem that is particularly high in perioperative patients. Epidemiological data suggest that individuals with insomnia exhibit more anxiety symptoms and similarly individuals with anxiety are more likely to suffer insomnia [12, 13]. Data collected from 997 patients undergoing elective surgery from 12 hospitals in China showed that higher preoperative anxiety (STAI-S > 44) was associated to poorer postoperative sleep quality [odds ratio (OR) = 1.79, 95% confidence interval (CI) = 1.17–2.76, p = 0.008) [14]. A retrospective cohort study recruited 299 noncardiac surgery patients with a mean age of 55 years and revealed that the incidence of insomnia at 3 days postoperatively was 26.1% (78/299). Logistic regression further showed that a higher preoperative GAD-7 score was a risk factor for insomnia after surgery (95% CI = 1.041–1.218, p = 0.003) [15]. Another prospective cohort study of 107 patients undergoing primary total joint arthroplasty indicated that 31% of patients exhibited poor sleep quality at 4, 8 and even 12 weeks postoperatively. Multivariate logistic regression analysis revealed that patients with a higher Zung Self-Rating Anxiety Scale (SAS) score suffered more from sleep disturbance (OR = 1.462, 95% CI = 1.171–1.825, p = 0.001) [16]. Postoperative insomnia not only increases the use of opioid consumption, but also increases the incidence of postoperative pain and delirium, which seriously affect the recovery of patients and diminish their satisfaction [17,18,19]. Therefore, reducing preoperative anxiety may have a critical impact on improving postoperative insomnia.

3 Preoperative anxiety and postoperative pain

Postoperative pain is a common but often inadequately treated condition. Numerous studies have suggested that preoperative anxiety not only increases the consumption of intraoperative anesthetics and vasoactive drugs, but also increases the usage of postoperative analgesics and is positively correlated with postoperative acute and chronic pain [10, 20]. A prospective study of 100 patients undergoing laparoscopic hysterectomy showed that the average preoperative anxiety score (evaluated with the SAS) was 40.99 ± 55 points, which was higher than the norm (29.78 ± 46) in China. The correlation coefficients between preoperative anxiety scores and postoperative pain scores in two different groups were 0.836 and 0.870 respectively, presenting with a markedly positive correlation [21]. An institutional-based prospective cohort study demonstrated that patients with high preoperative anxiety (STAI > 44) experienced obviously increased postoperative pain at 2, 4, 6 and 12 h, with p values of 0.012, 0.01, 0.001 and 0.002 respectively. The total tramadol consumption of 24 h in patients with high anxiety levels was 156.5 ± 23.4 while in patients with low anxiety levels, it was 147.1 ± 39.0, with a p value of 0.036 [22]. In addition, a prospective study from 194 consecutive patients who underwent glaucoma surgery showed that preoperative anxiety (evaluated with the SAS) was associated with increased clinically significant postoperative pain (OR = 4.13, 95% CI = 1.29–13.2, p = 0.017) [23]. It is well known that the consequences of suboptimal postoperative pain control include persistent postsurgical pain, prolonged duration of opioid use, delayed recovery time, impaired physical function, increased length of hospital stay and health care costs [24,25,26]. Thus, it is of great significance to decrease preoperative anxiety levels to reduce postoperative pain and analgesic consumption.

4 Preoperative anxiety and postoperative nausea and vomiting

Nausea and vomiting are the most common adverse events after surgery under general anesthesia, even above pain. However, there are few relevant studies on the relationship between preoperative anxiety and postoperative nausea and vomiting (PONV), and the results are inconsistent. A prospective study enrolled 200 consecutive patients who underwent ambulatory hand surgeries under general anesthesia and illustrated that PONV during the first 24 h after surgery was associated with a high level of preoperative anxiety (assessed using APAIS) in these patients (r = 0.301, p = 0.017) [27]. A retrospective cohort study of 8665 outpatients undergoing cancer surgery revealed that patients with preoperative anxiety had higher rates of adverse outcomes including PONV (adjusted difference 1.8%, 95% CI = 0.12%–3.4%, p = 0.029) [28]. These results indicated that preventing one instance of PONV would require treating at least 30 patients for anxiety. Moreover, a cross-sectional study enrolled 51 unpremeditated children (5–16 years old) undergoing outpatient surgery and showed that children's anxiety in the preoperative holding area has no predictive value for the occurrence of PONV in the post-anesthesia care unit or 24 h postoperatively [29]. In addition, a recent study also indicated that the correlation between preoperative anxiety and PONV was not statistically significant [14]. Although the relationship is not entirely clear, several complications caused by PONV such as wound dehiscence, aspiration, elevated intracranial pressure, health care costs and patient satisfaction still need to be considered.

5 Preoperative anxiety and postoperative neurocognitive dysfunction

Decline in cognitive ability is a common complication experienced in the postoperative period by adults, especially elderly individuals. Currently, all forms of related cognitive impairment are called perioperative neurocognitive disorder (PND) rather than postoperative cognitive dysfunction (postoperative cognitive dysfunction, POCD), as previously described [30, 31]. PND includes short-term disturbances (postoperative delirium, POD) and long-term disturbances (POCD) [32, 33]. It is well known that POD or POCD is associated with an increased rate of almost any postoperative complication, prolonged hospital stays, increased care dependency, a decrease in functional state, and a long-term increase in morbidity and mortality [34, 35]. Moreover, preoperative anxiety has been shown to detrimentally affect patients cognitively [36].

POD, is a syndrome characterized by an acute change in attention, awareness and cognition after surgery, which includes alterations in consciousness and disorganized thinking [37, 38]. A growing body of research has uncovered the close association between preoperative anxiety and POD in recent years. A prospective cohort study enrolled 372 adults undergoing total hip arthroplasty demonstrated that patients with anxiety had a higher incidence of POD than patients without anxiety (25.3% vs. 14.8%, OR = 0.51, 95% CI = 0.92–0.29, p = 0.025) [39]. Another prospective observational cohort study of elderly patients (aged 65 years or older) undergoing elective orthopedic surgery illustrated that preoperative anxiety was independently associated with POD (OR = 3.119, 95% CI = 1.144–8.500, p = 0.026) [40]. There was also a retrospective study that demonstrated anxiety was an independent predictor of POD in older patients undergoing elective surgery for lumbar disc herniation (OR = 2.228, 95% CI = 1.494–3.416, p = 0.009) [41]. Studies of other types of surgery have reached similar conclusions [42,43,44]. However, a few studies have also identified no significant association between them [45, 46]. The possible reasons for explanation were the difficulties in operationalization, measurement of preoperative anxiety or patients with good premorbid cognitive and functional status.

Unlike POD, POCD refers to a persistent rather than a transient state of cognitive dysfunction that occurs subsequent to surgery and anesthesia [47, 48]. To date, no direct evidence has suggested that there is a definite relationship between preoperative anxiety and POCD. A secondary data analysis of POCD in a cohort study of patients ≥ 65 undergoing elective noncardiac surgery demonstrated that preoperative anxiety symptoms were related to physical state rather than a harbinger of early cognitive decline [49]. Moreover, a prospective cohort study enrolled 26 older participants (mean age = 70 years, standard deviation = 8 years) who were scheduled for cochlear implantation has illustrated that no significant risk factors (including preoperative anxiety) were identified besides an effect of age on POCD [50]. Although reducing preoperative anxiety may provide an effective strategy for preventing PND, more high-quality evidence is needed.

6 Preoperative anxiety and other adverse events

In addition to the above adverse events, preoperative anxiety is also a negative factor affecting postoperative recovery. On the one hand, preoperative anxiety may give rise to perioperative hypertension, sinus tachycardia, myocardial ischemia and other cardio-cerebral vascular accidents, which can cause an increase in hospitalization expense and extension of hospitalization time [51]. On the other hand, preoperative anxiety also elicits the secretion of catecholamines and glucocorticoids in patients and further increases the risk of infection as well as delays wound healing [52]. In addition, although high levels of anxiety have been presented in few patients anticipated in cardiac surgery, these confer a strong and independent heightened risk of mortality or major morbidity [53]. Moreover, preoperative anxiety in young children undergoing surgery is associated with a more painful postoperative recovery and a higher incidence of sleep disorders, delirium and other problems [54]. Thus, preoperative anxiety has many effects on perioperative prognosis and outcome, so it is necessary to conduct appropriate interventions.

7 Intervention strategies for preoperative anxiety

Currently, effective interventions to treat or prevent preoperative anxiety are being actively explored to decrease the development of postoperative adverse events. Such interventions mainly include pharmacotherapies and nonpharmacotherapies.

7.1 Pharmacotherapy

Pregabalin is a gabapentinoid that has been widely used for the treatment of seizures and pain [55]. Additionally, as an adjuvant of opioids, it can also reduce opioid consumption when used in combination [56]. Recently, a systematic review and meta-analysis illustrated that there was moderate evidence of the efficacy of gabapentinoids in anxiety states [mean difference (MD) = −0.55, 95% CI = −0.92 – −0.18) [57]. An earlier prospective, randomized and controlled study conducted in consenting patients who underwent elective craniotomy for brain tumor resection demonstrated that perioperative use of twice-daily 150 mg pregabalin could attenuate preoperative anxiety, improve perioperative sleep quality, and reduce postoperative pain scores and analgesic usage without increasing the rate of adverse effects [58]. Another prospective, randomized and controlled study revealed that pregabalin was effective in reducing preoperative anxiety and that 150 or 300 mg pregabalin was associated with reduced blood pressure fluctuations after intubation, but with no significant differences between the two dose groups [59]. A similar study also directly presented that 150 mg of pregabalin was effective in attenuating preoperative anxiety and stress responses to endotracheal intubation [60].

Perioperative benzodiazepines are administered because of their anxiolytic, sedative and amnestic effects [61]. The use of midazolam as premedication for inducing anxiolysis before surgical procedures is widely accepted. In a double-blinded randomized clinical trial, investigators enrolled 90 participants aged 2–6 years who were scheduled for elective ear-, nose-and-throat surgery. Compared to oral clonidine (4 µg/kg) or intranasal dexmedetomidine (2 µg/kg), preschool children who took midazolam orally (0.5 mg/kg) resulted in more effective anxiolysis and less sedation [62]. A prospective, randomized and placebo-controlled study enrolled 88 patients scheduled for outpatient surgery and revealed that intravenous midazolam (0.04 mg/kg) was an effective anxiolytic and fewer patients in the midazolam group experienced postoperative vomiting than placebo group patients (8% vs. 21%) [63]. Alprazolam, a new short-acting benzodiazepine, has been confirmed earlier to be an effective alternative to midazolam for anxiety reduction without causing amnesia [64, 65]. Seventy-five patients scheduled for abdominal hysterectomy under general anesthesia were included in a randomized, placebo-controlled study. Oral alprazolam (0.5 mg 2 h prior to surgery) provided significant anxiolysis and showed no opioid sparing effects postoperatively compared to placebo. However, we must pay attention to the impairment of psychomotor function in the early postoperative period [64].

Melatonin, a naturally occurring hormone, has been confirmed to offer an alternative treatment to benzodiazepines for ameliorating anxiety conditions in the perioperative period [2, 66]. Madsen et al. carried out a systematic meta-analysis including 27 randomized controlled trials and 2319 participants to assess the use of melatonin for treating perioperative anxiety. They pointed out that melatonin could effectively reduce preoperative anxiety (MD = −11.69, 95% CI = −13.80 – −9.59) and had less interference with psychomotor and cognitive function than benzodiazepines [2]. In addition, a double-blind randomized clinical trial demonstrated that melatonin (5 mg prolonged-release oral capsules) was an effective alternative to manage anxiety and could help to reduce intraoperative midazolam consumption and hospital stay in women undergoing total abdominal hysterectomy [67]. Moreover, a randomized and placebo-controlled trial also showed that compared with oral midazolam (0.3 mg/kg), a multimodal anxiolytic approach with oral melatonin (0.3 mg/kg) could markedly reduce preoperative anxiety and postoperative delirium in children 3 to 8 years who received sevoflurane anesthesia for elective ambulatory procedures [68].

Dexmedetomidine is a highly selective α2-adrenergic receptor agonist that is associated with sedative and analgesic sparing effects as well as reduced delirium and anxiety. Recent research has shown that dexmedetomidine could improve the preoperative anxiety of patients undergoing carotid artery stenting and achieve a sufficient sedation effect without causing postoperative cognitive dysfunction [69]. Moreover, when compared with midazolam, dexmedetomidine was effective in decreasing preoperative anxiety upon separation from parents [risk ratio (RR) = 1.30 (1.05–1.62), p = 0.02] [70]. Unlike oral or intravenous administration, intranasal dexmedetomidine eliminates the need for venous opening, pain and other side effects such as infection and anaphylaxis in patients [71, 72]. A prospective, randomized and controlled trial indicated that intranasal dexmedetomidine could safely and effectively improve the preoperative anxiety and insomnia condition of patients with insomnia and anxiety [73]. In addtion, another prospective study also illustrated that intranasal dexmedetomidine premedication was more effective than oral midazolam to reduce preoperative anxiety in pediatric patients (2–12 years of age) [74]. Thus, intranasal dexmedetomidine may be used as a complementary therapy for preoperative anxiety.

7.2 Nonpharmacotherapy

Aromatherapy is a form of holistic healing treatment that uses essential oils or aromas to improve persons’ emotional and physical conditions. The pooled results from a systematic meta-analysis demonstrated that aromatherapy with different essential oils could alleviate anxiety significantly regardless of the reason for anxiety. The weighted MD was −5.16 for the STAI-S (95% CI = −5.78 – −4.55, p < 0.001) and −2.85 for the STAI-T (95% CI = −3.95 – −1.75, p < 0.001) [75]. Another meta-analysis indicated that aromatherapy could significantly ameliorate preoperative anxiety (standard MD = −0.57, 95% CI = −0.75 – −0.39, p < 0.00001) for adults awaiting surgical procedures, compared to placebo control, conventional care and no intervention. Short-length (≤ 20 min per session) aromatherapy inhalation seemed to be more worthy of being recommended in clinical settings [76]. In addition, a randomized trial determined that aromatherapy could reduce anxiety when administered to women (≥ 18 years) before undergoing breast surgery despite no significant changes in vital signs [77].

Music therapy is the clinical use of music to accomplish individualized goals such as reducing stress and improving mood and anxiety. It has been suggested that preoperative music exposure was effective in reducing anxiety level and self-reported pain on intra- and post-operative pain during cataract surgery [78]. A prospective, randomized and controlled trial illustrated that listening to patient-preferred favour music preoperatively can reduce anxiety, regulate hemodynamic parameters and improve postoperative patient satisfaction [79]. A recent randomized controlled study showed that music therapy might be a viable complementary modality to usual surgical care in the gynecologic setting for its ability to significantly decrease preoperative anxiety in women undergoing total laparoscopic hysterectomy for benign conditions [80].

Massage therapy is a traditional technique in China and it can prompt the release of hormones and provide a feeling of ease to relieve tension and anxiety. A recent study revealed that foot massage is effective in alleviating pain and anxiety while improving quality of life in patients undergoing anterior cervical discectomy and fusion [81]. Moreover, machine-based hand massage significantly reduces anxiety in patients awaiting ambulatory surgery while not significantly affecting their vital signs [82]. Furthermore, aromatherapy massage with lavender oil increases sleep quality and reduces the level of anxiety in patients with colorectal surgery in the preoperative period [83].

Other forms of relaxation also reveal good anxiolytic effects. Guided imagery is a free stress-relieving therapy and, with practice, can be done just about anywhere. A randomized, triple-blind clinical trial illustrated that guided imagery relaxation therapy was an effective nursing intervention for the reduction of state anxiety and blood cortisol levels in the preoperative period in patients undergoing video-laparoscopic bariatric surgery [84]. Hypnosis is a modified state of consciousness that is different from normal consciousness and sleep stages. A randomized controlled trial revealed that hypnosis intervention significantly alleviated patients’ anxiety levels before entering the operating rooms [85]. In addition to the methods mentioned above, acupuncture, virtual reality and proper exercise are also noninvasive and nondrug intervention methods that have been reported to effectively reduce preoperative anxiety [51, 86, 87]. However, further research is needed to address the effective use of nonpharmacotherapies in the management of preoperative anxiety.

8 Summary and outlook

As one of the most common clinical problems in perioperative patients, preoperative anxiety is closely related to the occurrence of postoperative adverse events. Many clinical studies have confirmed that preoperative anxiolytic interventions can effectively reduce the occurrence of postoperative adverse events. Therefore, paying more attention to patients' preoperative anxiety and taking more effective actions will help ensure the safety of patients and improve their satisfaction. Nevertheless, due to their complicated relationship, studies on the mechanisms of preoperative anxiety affecting postoperative adverse events are relatively rare. Therefore, exploring the exact mechanisms and identifying new therapeutic targets should be priorities for future work.