Psychological stress has been shown to impair wound healing, but experimental research in surgical patients is lacking. This study investigated whether a brief psychological intervention could reduce stress and improve wound healing in surgical patients. This randomised controlled trial was conducted at a surgical centre. Inclusion criteria were English-speaking patients over 18 years booked to undergo elective laparoscopic cholecystectomy; exclusion criteria were cancellation of surgery, medical complications, and refusal of consent. Seventy five patients were randomised and 15 patients were excluded; 60 patients completed the study (15 male, 45 female). Participants were randomised to receive standard care or standard care plus a 45-min psychological intervention that included relaxation and guided imagery with take-home relaxation CDs for listening to for 3 days before and 7 days after surgery. In both groups ePTFE tubes were inserted during surgery and removed at 7 days after surgery and analysed for hydroxyproline as a measure of collagen deposition and wound healing. Change in perceived stress from before surgery to 7-day follow-up was assessed using questionnaires. Intervention group patients showed a reduction in perceived stress compared with the control group, controlling for age. Patients in the intervention group had higher hydroxyproline deposition in the wound than did control group patients (difference in means 0.35, 95% CI 0.66–0.03; t(43) = 2.23, p = 0.03). Changes in perceived stress were not associated with hydroxyproline deposition. A brief relaxation intervention prior to surgery can reduce stress and improve the wound healing response in surgical patients. The intervention may have particular clinical application for those at risk of poor healing following surgery.
A systematic review has shown that psychological stress impairs wound healing across a variety of laboratory and clinical settings (Walburn et al., 2009). Dermal punch biopsy wounds heal more slowly in women caring for relatives with Alzheimer’s disease than in matched control subjects, and mucosal punch biopsy wounds heal more slowly in students during exams than during vacation time (Kiecolt-Glaser et al., 1995 and Marucha et al., 1998). Diabetic foot ulcers heal more slowly in depressed patients, and surgical wounds show impaired healing in patients with higher stress levels in the month prior to surgery (Broadbent et al., 2003, Cole-King and Harding, 2001, Monami et al., 2008 and Vedhara et al., 2010). Higher cortisol levels may play a role in the relationship between stress and slower healing by down-regulating the immune system (Ebrecht et al., 2004). Local inflammatory cells, and pro-inflammatory cytokines including interleukin-1, have been shown to be lower in the wounds of highly stressed individuals (Glaser et al., 1999).
This evidence points to the potential for psychological interventions to improve wound healing. A recent study has shown that emotional disclosure improves the healing of punch biopsy wounds in healthy males, although no changes in depression or stress were achieved (Weinman et al., 2008). Psychological interventions may be particularly applicable for surgical patients, where poor wound healing can have serious consequences (Galat et al., 2009). Meta-analysis has shown psychological preparation for medical procedures can reduce distress, pain, and length of hospital stay (Devine, 1992). In terms of physiological indices, relaxation and guided imagery have improved anxiety, and reduced urinary cortisol and wound erythema amongst cholecystectomy patients, but the effect on physiological indices of wound healing has not been assessed (Holden-Lund, 1988).
Wound healing proceeds as a cascade with the later stages involving the deposition of collagen, which restores strength and function to damaged tissue (Hunt and Hopf, 1997). The ePTFE model measures collagen synthesis as an index of healing through the assessment of hydroxyproline deposited in high porosity tubing (Goodson and Hunt, 1982). Hydroxyproline is an amino acid that gives stability to the triple helix structure of collagen (Prockop et al., 1979), and has been used as a marker of collagen synthesis, and therefore a marker of the proliferative phase of wound healing. Hydroxyproline levels have also been shown to correlate with the tensile strength of wounds, which is of clinical relevance (Wicke et al., 1995). Reduced hydroxyproline deposition occurs with corticosteroid therapy (Wicke et al., 1995), which provides further basis for suggesting that psychological stress and stress hormones might impair wound healing. The ePTFE method has been used previously in surgical studies to investigate the influence of anaemia (Jensen et al., 1986), pre-operative illness (Goodson et al., 1987), recent food intake (Windsor et al., 1988), and tissue oxygenation (Jonsson et al., 1991) on wound healing. It has also been used to test the effectiveness of peri-operative interventions on wound healing. For example, immunonutrition has been shown to increase levels of hydroxyproline in surgical patients (Farreras et al., 2005 and Williams et al., 2002).
This study aimed to investigate whether a psychological intervention to reduce stress could improve the deposition of hydroxyproline in surgical wounds. Elective laparoscopic cholecystectomy patients were selected because the operation is common, of moderate magnitude, and the acute phase response is short lived and well characterised. The psychological intervention was based on the study by Holden-Lund (1988). We hypothesised that patients who received the psychological intervention would demonstrate higher concentrations of hydroxyproline at the wound site than would the control group.
