Shivering is characterized by rapid, rhythmic muscle contractions in response to cold exposure or pathological conditions and represents a crucial mechanism by which the thermoregulatory system maintains core body temperature. POS commonly occurs during emergence from anesthesia, with a reported incidence of 60%–80%. Its development results not only from hypothermia but is also closely associated with the effects of anesthetic agents, surgical trauma, and stress responses (7). Shivering significantly increases oxygen consumption by 20%–35% and elevates the basal metabolic rate by 100%–300%. These physiological changes may lead to hypoxemia, acidosis, and even myocardial ischemia, thereby posing heightened risks, particularly for elderly patients and those with compromised cardiopulmonary reserve (8). Furthermore, shivering can exacerbate incisional pain, impede postoperative recovery, increase the risk of infection, and thereby adversely affect postoperative outcomes and patient safety (9).

The growing adoption of the ERAS protocol has heightened clinical attention toward the accurate assessment and effective reduction of POS. The assessment of shivering has gradually evolved from subjective scales to objective technologies. Among traditional evaluation tools, the methods established by Crossley and Mahajan primarily assess shivering intensity based on observations of peripheral vasoconstriction, peripheral cyanosis, and patterns of muscle activity. The Mathew scale emphasizes the evaluation of the intensity of fasciculations and muscle activity localized to the facial and cervical regions. Conversely, the bedside shivering assessment scale (BSAS) evaluates the distribution of shivering through visual inspection and palpation of the neck, chest, arms, and legs. The BSAS, with its established reliability and validity, has been widely adopted as an internationally accepted standard for evaluating shivering (10). Recent breakthroughs in sensor and artificial intelligence technologies have significantly advanced the objectivity and precision of shivering assessment. For instance, computer vision-based algorithms for analyzing muscle tremors can now detect characteristic rhythmic muscle contractions in real time, within a frequency range of 0.5–8 Hz. Studies have demonstrated that this approach can achieve an accuracy of up to 92.3% in identifying shivering episodes (11). Furthermore, by integrating multimodal data from infrared thermal imaging, accelerometers, and photoplethysmography (PPG), integrated wireless monitoring platforms enable comprehensive assessment and early warning of shivering. In the field of objective TCM research, Zhang Qian and colleagues investigated the use of deep learning to analyze TCM signs to assist in shivering recognition. They developed an intelligent tongue-pulse diagnosis system capable of identifying signs of Yang deficiency with cold congelation, such as a pale, swollen tongue and a deep, slow, and weak pulse. This system reportedly demonstrates a predictive performance for shivering risk, with an AUC of 0.87 (12). This work paves a promising new avenue for integrating the principles of TCM pattern differentiation into the perioperative risk assessment framework (Table 1).

Although “perioperative shivering” is not classified as a designated disease entity in TCM, its clinical presentation aligns with classical TCM disorders like “zhan li” (trembling) and “han jue” (cold limbs). The core pathology involves compromised Yang Qi, leading to inadequate bodily warming. The Plain Questions: On Regulating the Meridians elucidates the pathogenesis by stating, “Yang insufficiency results in external cold,” affirming that the deficiency of Yang Qi is the fundamental cause of cold intolerance and trembling. The “Treatise on Cold Damage Diseases” also repeatedly discusses the relationship between shivering and the stagnation or decline of Yang Qi. Surgical trauma and anesthetic agents are particularly prone to impairing the body's vital Qi, especially Yang Qi. Zhang Jingyue of the Ming Dynasty stated in Jingyue Quanshu: “The Vital Gate (Mingmen) is the root of Primordial Qi (Yuanqi) and the abode of Water and Fire; the Yin Qi of the five Zang organs cannot be nourished without it, nor can the Yang Qi of the five Zang organs be activated.” This emphasizes that the fire of the Vital Gate is the foundation of the body's entire Yang Qi. Postoperative depletion of Yang Qi and decline of the Mingmen fire result in an inability to warm the tendons and limbs, thereby leading to the onset of shivering.

Consequently, TCM identifies the etiology of postoperative shivering as fundamentally characterized by Yang Qi deficiency and weakened Mingmen fire, potentially compounded by excess manifestations such as cold congelation or blood stasis. The therapeutic principle is therefore to warm Yang, dispel cold, tonify the fire (of Mingmen), and support Yang. This approach is well exemplified by the classic formula Shen Fu Tang.

In addition to Yang Qi deficiency, constraint or stagnation of Yang Qi (Yang Qi Yu Zhi) represents another pivotal etiological pattern within TCM theory. The Treatise on Cold Damage Diseases delineates scenarios in which Yang Qi, although not deficient, becomes obstructed in its dispersing and warming functions, leading to impaired heat distribution and consequent shivering. This pattern often arises from pathogenic factors that disrupt the Shaoyang pivot mechanism or from internal obstructions by phlegm-dampness or blood stasis, which impede the free flow of Qi (13). In such cases, defensive Yang fails to properly reach the body surface, resulting in alternating chills and fever or shivering without true hypothermia. Within the perioperative context, factors such as anesthetic suppression, surgical trauma, emotional stress, or pre-existing Qi stagnation may contribute to a similar state of Yang constraint. The therapeutic strategy for this pattern shifts from pure supplementation to promoting Qi movement and unblocking stagnation, employing principles such as harmonizing Shaoyang and promoting Qi circulation, as embodied in formulas like Xiao Chaihu Tang (Minor Bupleurum decoction) (14). This broader conceptualization underscores that shivering in TCM is not monolithic but rather encompasses both deficiency and stagnation patterns of Yang dysfunction, thereby enriching the holistic diagnostic framework.

Shivering is a vital physiological response to hypothermia or pathological conditions and has traditionally been understood as being initiated by an elevation of the hypothalamic thermoregulatory set point. This elevation, in turn, triggers involuntary, rhythmic contractions of the skeletal muscles via motor pathways, a process aimed at generating heat and maintaining core body temperature. However, emerging evidence indicates that the mechanism of shivering is not confined to central regulation but rather involves a multilevel, networked physiological process encompassing peripheral tissue energy metabolism, mitochondrial function, and neuroendocrine regulation.

Mitochondrial complex I (CI), the key initiating enzyme in the electron transport chain responsible for catalyzing NADH oxidation, generates a proton gradient that serves as the fundamental driver of ATP production. During episodes of shivering, skeletal muscle energy demands increase dramatically, necessitating highly efficient ATP generation that is dependent on complex I (15). Research has demonstrated that dysfunction of complex I is a key contributor to insufficient heat production during shivering episodes, with the NDUFS2 subunit playing a critical role. Located near the ubiquinone (CoQ) binding site, NDUFS2 is essential for the assembly, stability, and catalytic activity of the complex. Downregulation or functional inhibition of NDUFS2 severely impairs complex I activity, leading to reduced proton pumping efficiency, a decline in mitochondrial membrane potential, and ultimately compromised function of ATP synthase (complex V), resulting in insufficient ATP supply (16). Under such conditions, even when a shivering response is present, skeletal muscle experiences an energy crisis that produces weak and ineffective contractions, manifesting as “shivering without heat production.”

Beyond the direct impairment of energy production, dysfunction of complex I can also induce severe secondary damage. When electron transfer is obstructed, electrons are prone to leak from specific sites within complex I (e.g., the I_Q site) and react with oxygen molecules, generating a surplus of superoxide and initiating oxidative stress. This not only exacerbates damage to mitochondrial structure and function, harming muscle cells, but also forms a vicious cycle with the ongoing energy crisis. Concurrently, the resulting imbalance in the NADH/NAD+ ratio disrupts multiple metabolic pathways, including glycolysis and the tricarboxylic acid (TCA) cycle, leading to global metabolic disturbances within the cell. Importantly, the body is not defenseless against a surge in ROS. In tissues such as skeletal muscle, uncoupling proteins (e.g., UCP3) can be activated to induce “mild uncoupling,” which lowers the mitochondrial membrane potential and thereby provides negatively feedback to suppress excessive ROS generation. This represents a crucial self-protective mechanism under cellular stress (17). Beyond the intracellular energy crisis, the systemic neuro–immune–inflammatory response also plays a critical role in the initiation and maintenance of POS.

This systemic metabolic disturbance further exacerbates shivering insufficiency through several direct and indirect pathways. First, impairment of glycolysis and the TCA cycle reduces the availability of pyruvate and NADH, which are key substrates for mitochondrial ATP synthesis. Consequently, even when shivering commands are centrally initiated, skeletal muscle faces an exacerbated energy crisis, leading to weaker and less effective thermogenic contractions (18). Second, the accumulation of metabolic intermediates—such as lactate and acyl-carnitines—alters intracellular pH and ion homeostasis, potentially disrupting excitation–contraction coupling in muscle fibers (19). Third, systemic metabolic dysregulation can influence the synthesis and release of neurotransmitters, including serotonin and catecholamines, which are integral to central thermoregulation and peripheral vasomotor tone (20). Thus, the metabolic consequences of complex I dysfunction not only undermine cellular energy production but also disrupt the integrated neuro-metabolic network required for effective shivering thermogenesis.

Recent studies have identified activation of the “brain–immune axis” as a core mechanism in the pathophysiology of POS, particularly for the inflammatory subtype. Specifically, surgical trauma and anesthetic agents can activate the “neuro–immune–inflammatory axis,” which disrupts the hypothalamic thermoregulatory set point through the following pathways.

The prostaglandin E2 (PGE2) pathway: This represents the primary pathway. Peripheral tissue injury activates cyclooxygenase-2 (COX-2), leading to substantial synthesis of PGE2 within the anterior hypothalamus. PGE2 binds to the EP3 receptors in the hypothalamus, which elevates the thermoregulatory set point by inhibiting warm-sensitive neurons and exciting cold-sensitive neurons. This represents one of the most direct neuroimmune signals responsible for the trigger of shivering (21).

The HMGB1/TLR4/NF-κB pathway: High-mobility group box 1 (HMGB1), as a key damage-associated molecular pattern (DAMP), is released from injured cells and activates Toll-like receptor 4 (TLR4), thereby triggering the downstream nuclear factor kappa B (NF-κB) signaling. This cascade promotes the synthesis and release of pro-inflammatory cytokines, such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) (22). These inflammatory cytokines not only exacerbate the systemic inflammatory response but can also act on the hypothalamus by crossing the blood–brain barrier or via vagal afferent signaling. As a result, the thermoregulatory set point is further elevated, generating an “inflammatory storm” that promotes shivering (23).

This neuro–immune–inflammatory axis interacts closely with the aforementioned mitochondrial–BAT thermogenic axis. On one hand, inflammatory signals such as TNF-α can directly inhibit the activity of mitochondrial complex I. Therefore, central immune–inflammatory signals orchestrate the initiation of shivering, while the functional state of peripheral mitochondria and brown adipose tissue (BAT) dictates the efficiency and effectiveness of thermogenesis. Together, these two components constitute the complete pathophysiological framework underlying POS.

In the body's defense against cold exposure, thermogenesis is achieved not only through shivering, which is primarily mediated by skeletal muscle contractions, but also through non-shivering thermogenesis mediated by uncoupling protein 1 (UCP1) in brown adipose tissue (BAT). Together, these mechanisms constitute a multilayered and complementary strategy for maintaining body temperature (24, 25). In contrast to ATP-dependent heat production in shivering, UCP1 operates by uncoupling substrate oxidation from ATP synthesis, dissipating energy directly as heat. Although the capacity for UCP1-dependent non-shivering thermogenesis in adults is relatively limited overall, it serves as an important supplement to shivering thermogenesis and may play a particularly significant role under specific conditions. A dysfunction in any component of either mechanism can lead to inadequate heat production under cold stress (26).

Furthermore, surgical trauma and other stress conditions can activate inflammatory responses, leading to the release of pro-inflammatory cytokines such as IL-6 and TNF-α. These cytokines act on the hypothalamus to alter the thermoregulatory set point, thereby promoting the initiation of shivering. In addition, neurotransmitter systems are involved. For instance, abnormal release of catecholamines and serotonin (5-HT) can affect central thermoregulation and peripheral vasoconstriction, thereby further modulating the intensity and duration of shivering (27).

In summary, shivering is a complex response initiated centrally and rely on the coordinated execution of peripheral energy metabolism and cellular/molecular functions. Greater emphasis should be placed on multidimensional investigations into mitochondrial function and the neuro–endocrine–immune network to provide novel insights into the clinical prevention and management of shivering-related complications.

The “fire of the Mingmen” (vital gate) in TCM, considered the foundation of the body's Yang Qi, serves a “warming function.” This physiological role aligns directly with the organism's goal of maintaining core body temperature through heat production. Modern research has elucidated that mitochondrial energy metabolism—particularly the function of complex I—and UCP1-mediated non-shivering thermogenesis in brown adipose tissue represent central biological mechanisms for maintaining body temperature. Notably, Chinese herbal medicinals with functions such as “warming Yang to dispel cold and tonifying fire to reinforce Yang”—including Shenfu injection and cinnamon extract—have been shown to exhibit modern pharmacological actions that precisely target key nodes within these established modern thermoregulatory pathways. This convergence demonstrates that, despite employing distinct theoretical frameworks, TCM and Western medicine share a common understanding of the pathological essence of shivering and its therapeutic management. Such alignment provides a theoretical basis for their synergistic application, positing that Yang-warming herbs can simultaneously modulate both energy metabolism and neuroimmune responses, thereby enabling a multitarget regulatory strategy (Figure 1).

The TCM approach emphasizes the core principles of warming and tonifying Yang Qi, dispelling cold, and unblocking the meridians. The classic formula Shenfu Tang (ginseng and aconite decoction), documented in the Shi Yi De Xiao Fang (Effective Formulas from Generations of Physicians), serves as a representative prescription. In this formulation, ginseng greatly tonifies primordial qi, while aconite warms the kidney and reinforces Yang, thereby jointly restoring Yang and rescuing collapse. Modern research has not only validated its classical efficacy but also further elucidated its scientific basis at the core level of energy metabolism. Studies have shown that the active components of Shenfu injection upregulate the expression of sirtuin 1 (SIRT1), thereby activating the downstream key factor peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α). This signaling cascade effectively promotes mitochondrial biogenesis and enhances the functional activity of mitochondrial respiratory chain complexes (28). As a master regulator of mitochondrial biogenesis, PGC-1α activation significantly promotes the generation of new mitochondria and enhances the functional activity of mitochondrial complex I, thereby efficiently elevating cellular ATP production (29). This mechanism, which targets the cell's power plant (mitochondria), provides solid molecular evidence for the TCM theory of “tonifying the fire of the Mingmen (vital gate).” The SIRT1/PGC-1α signaling axis effectively bridges the ancient concept of reinforcing primordial Yang with contemporary mitochondrial biology, demonstrating how Yang-warming herbs enhance energy metabolism at the subcellular level.

For patterns characterized by cold congelation and blood stasis, Danggui Sini Tang (Angelicae sinensis decoction for frigid extremities), with appropriate modifications, can be selected to warm the meridians, dispel cold, nourish the blood, and unblock the vessels. Modern pharmacological studies reveal that the therapeutic effects of this formula extend beyond simple warming and unblocking effects, directly targeting the neuro–immune–inflammatory core implicated in the pathogenesis of POS. Research has demonstrated that Danggui Sini Tang not only significantly reduces plasma prostaglandin E2 (PGE2) and serum interleukin-6 (IL-6) levels—effectively inhibiting the inflammatory upward shift of the central thermoregulatory set point—but also ameliorates microcirculatory dysfunction, thereby ensuring adequate energy supply to peripheral tissues and facilitating the clearance of metabolic waste products (30). Through these two synergistic dimensions—anti-inflammatory effects and improved tissue perfusion—the modern scientific basis underlying the formula's classical function of “warming the meridians and dispelling cold” is collectively elucidated.

As a distinctive external therapy in TCM, TEAS has recently become a research focus due to its non-invasive nature, proven efficacy, and ability to alleviate perioperative complications, including anxiety, gastrointestinal dysfunction, and pain (31). A frequently selected acupoint is Zusanli (ST36). As the He-Sea point of the stomach meridian, it can be stimulated by both moxibustion and acupuncture to warm the middle jiao, tonify deficiency, and harmonize the Qi and blood (32). This demonstrates that, despite employing distinct theoretical frameworks, TCM and Western medicine share a common understanding of the pathological essence of shivering and its therapeutic management. Such alignment provides a theoretical basis for their synergistic application, positing that Yang-warming herbs can simultaneously modulate both energy metabolism and neuroimmune responses, thereby enabling a multi-target regulatory strategy: At the supraspinal level, signals generated by TEAS at ST36 are transmitted via Aβ and Aδ primary afferent fibers, which subsequently ascend to activate the key descending inhibitory pathway comprising the periaqueductal gray (PAG) and the rostral ventromedial medulla (RVM). This activation leads to the release of serotonin (5-HT) and norepinephrine to the spinal dorsal horn, which effectively suppresses the ascending transmission of noxious thermal signals, including those responsible for shivering (33). At the systemic immunomodulatory level, TEAS has been established as a potent activator of the “cholinergic anti-inflammatory pathway.” Afferent signals are transmitted via the vagus nerve, promoting the release of acetylcholine from nerve terminals. The subsequent binding of acetylcholine to the α7 nicotinic acetylcholine receptor (α7nAChR) on immune cells, such as macrophages, inhibits activation of the nuclear factor kappa-B (NF-κB), thereby significantly suppressing the release of pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α) (34). This mechanism provides a key explanation for the systemic and long-lasting anti-inflammatory and anti-shivering effects of TEAS.

Traditional Chinese medicine emphasizes the principle of “tailoring treatment to the individual, season, and locality” (three factors considerations). In clinical practice, personalized interventions must be implemented based on the patient's constitution and syndrome type. For patients with Yang Qi deficiency syndrome, characterized by an aversion to cold, cold limbs, pale complexion, and a deep-slow pulse, a recommended intervention is intravenous infusion of Shenfu injection combined with ginger-partition moxibustion at the Shenque (CV8) acupoint (35). For patients presenting with cold coagulation and blood stasis, which is characterized by cyanotic lips, cold extremities, and a purplish-dark tongue, a suitable therapeutic approach involves the use of modified Danggui Sini decoction complemented by pricking and cupping at the Xuehai (SP10) acupoint (36); Postoperative shivering in patients after cesarean section is primarily attributed to impairment of the Thoroughfare and Conception Vessels, characterized by Yang deficiency and blood depletion. The recommended treatment principle is to warm the channels and nourish the blood, employing moxibustion at Sanyinjiao (SP6) and Qihai (CV6) acupoints, combined with the oral administration of herbal formulas that warm the meridians and replenish blood (37). Through the synergistic integration of pharmacological and non-pharmacological approaches, TCM simultaneously addresses systemic regulation and local intervention, thereby demonstrating distinctive strengths in the prevention and treatment of POS.

The pharmacological strategy for managing POS in Western medicine has evolved from single-symptom control to multitargeted, precision-based interventions that address its complex mechanisms. In this context, the application of dexmedetomidine epitomizes the current cutting edge.

Starting with the integration of modern monitoring technologies and TCM diagnostic methods, this system achieves dynamic perception and early warning of shivering risk. By combining an artificial intelligence-based myotremor analysis system that detects rhythmic muscle contractions (0.5–8 Hz) with an intelligent tongue-pulse diagnostic device that identifies TCM signs of Yang deficiency (e.g., pale, swollen tongue, and a deep, slow, weak pulse), the model significantly enhances the sensitivity of shivering risk prediction. Once a high risk is flagged, the early warning system initiates multidimensional interventions.

A proposed synergistic drug strategy recommends a regimen combining dexmedetomidine with Shenfu injection. Prophylactic administration may include a low dose of dexmedetomidine (e.g., a small loading dose followed by continuous infusion at a low maintenance rate) during surgery or in the postanesthesia care unit, alongside intravenous infusion of Shenfu injection at standard clinical dosages. The specific dosing regimen and timing should be individualized based on the patient's body weight, physiological status, and intraoperative conditions (55). Dexmedetomidine exerts its antishivering effect by activating central α₂-adrenoceptors, whereas Shenfu injection, leveraging its components including ginsenosides, acts via multiple pathways. On one hand, it upregulates UCP1 expression via the β3-AR/cAMP pathway to enhance non-shivering thermogenesis. On the other hand, its holistic “warming Yang” effect contributes to the improvement of cellular energy metabolism. Neuro–immune modulation: Research has shown that applying 2/100 Hz TEAS at the Zusanli (ST36) acupoint (56) can activate the hypothalamic arcuate nucleus–nucleus tractus solitarius pathway, promote the release of endorphins, and inhibit the TLR4/NF-κB signaling pathway in the spinal dorsal horn. This thereby effectively reduces the levels of pro-inflammatory cytokines IL-6 and TNF-α, thus blocking the onset of inflammation-mediated shivering (57, 58).

Enhanced physical warming: A combination of a constant-temperature garment and an Orve+ wrap with a warming blanket is used, beginning with 30 min of prewarming. This approach establishes a dual thermoregulatory mechanism of “passive heat storage plus active regulation,” significantly reducing the incidence of hypothermia and associated shivering (59).

Addressing the key pathology of anesthetic-induced mitochondrial complex I dysfunction, we propose an integrated TCM–Western medicine intervention strategy centered on “preserving NDUFS2 subunit function and promoting non-shivering thermogenesis.” Studies have shown that aconite alkaloids and ginsenosides in Shenfu injection can partially reverse the suppression of mitochondrial function induced by anesthetics such as sevoflurane, thereby consolidating the “vital gate fire” at the molecular level (60). Concurrently, the novel benzodiazepine remimazolam, which exerts minimal inhibition of the mitochondrial respiratory chain and is metabolized independently of the P450 enzyme system, can be combined with Shenfu injection. This combination reduces the total sedative dose required, thereby lowering the risks of hypotension and respiratory depression, making it particularly suitable for elderly and frail patients (45). Moreover, cinnamon extract (cinnamaldehyde) activates the TRPV1 channel, directly stimulating brown adipose tissue and upregulating UCP1 expression by approximately 2.1-fold. This mechanism provides an alternative thermogenic pathway that bypasses mitochondrial complex I (61), offering a pharmacological basis for the modern application of the TCM principle “warming Yang to disperse cold.”