Table 1.

Summary of clinical studies of NPWTi-d-

Author (year)	Type of study	Diagnosis/type of injury	No. of patients	NPWTi-d- protocol	Solutions used	Final wound closure (duration)	Complications	Follow up
Leffler et al. [20] (2009)	Case series	Subacute/chronic osteomyelitis	6	Application of NPWTi-d- in chronic wounds and their outcomes	Polyhexanide	Six months post-surgery	No	After NPWTi-d-, bacterial swabs and tissue biopsies were sterile; after 3 to 10 months, there was no recurrence of osteomyelitis
Timmers et al. [21] (2009)	Prospective cohort study	Osteomyelitis of pelvis or lower limb	Case control cohort studies	2 cohorts; I: NPWTi + debridement/antibiotics, C: standard of care (surgical debridement, gentamycin polymethyl-methacrylate beads implantation, long-term IV antibiotics) I stands for V.A.C. Instill Polyhexanide Solution; Dwell time: 10–15 min; NP: 300–600 mmHg; Mean days of treatment: 6 to 60	Polyhexanide Gentamicin PMMA beads	Not available		The NPWTi-d- group underwent fewer operations and required a shorter stay in the hospital
Lehner et al. [22] (2011)		Infected orthopedic implants (THA 62.5%, TKA 31.3%, 6.2% osteosynthetic material)	32		Polyhexanide	Not available		86% (acutely infected) and 80% (chronically infected) of implants were retained
Brinkert et al. [23] (2013)		Various wound types that are infected or at high risk of infection (such as open fractures, infected hematomas, PUs, and non-healing postoperative dehiscence wounds)	Prospective case series to evaluate the outcomes of 131 patients with complex wounds treated with NPWTi-d-	NPWTi-d- case series; V.A.C. VeraFlo; Solution: Normal saline; Dwell time: 10 min; NP: 4–12 h; Pressure: 125 mmHg; Mean days of treatment: 12.2	Saline	12–19 days	No incidence of wound recurrence or dehiscence was observed at operated site	Wound closure was achieved in 128 of 131 (98%) wounds • With respect to filling dead space more rapidly and completely, NPWTi-d- using saline showed improved granulation tissue production compared with NPWT
Fluieraru et al. [24] (2013)		Complex wounds (such as vast undermining tracts or deep wounds) or infected wounds that did not respond to NPWT	Retrospective case series of 24 patients - 12 patients who had been unsuccessfully treated with NPWT - 12 patients with complex wounds	Case series for NPWTi-d-; V.A.C. Instillation; Solution: Sterile saline; Dwell time: 10 min; NP: 4 h; Pressure: 125 mmHg; Days of treatment: 6–15	Isotonic saline	After one month		The lower extremities of the patient who did not recover was too devascularized to granulate effectively. The main outcomes of instillation therapy in these patients included encouraging the growth of granulation tissue and filling weakened holes
Gabriel et al. [25] (2014)			Retrospective analysis comparing patients with NPWT (n = 34) with NPWTi-d- (n = 48) • A hypothetical economic model that compares patients with NPWT and NPWTi-d- utilising cost assumptions for debridement		Saline or polyhexanide	The NPWT-instillation-treated wounds were closed in 29.6 ± 6.5 days		Between NPWTi-d- and NPWT patients, there were significant differences (P 0.001) for the following: mean OR debridement (2.0 versus 4.4) - average length of hospital stay (8–1 vs. 27–4) - average LOT (4–1 versus 20–9) - Mean time to wound closure (4–1 days as opposed to 20–9) • The fictitious economic model suggested that there could be an average $8143 savings for OR debridement between NPWTi-d-($6786) and NPWT ($14 929) patients • The average cost of therapy varied between the two groups by $1418 ($799 for NPWTi-d- against $2,217 for NPWT)
Goss et al. [26] (2014)		A substantial bacterial bioburden (> 105 CFU/g tissue) is present in DFUs, VSUs, and other wound aetiologies	Prospective pilot research in 13 patients	Prospective contemporaneous cohort design; NPWT (C) vs. NPWTi-d- I: V.A.C. VeraFlo; C: Dakin's solution; Dwell time: 10 min; NP: 60 min; Pressure: 125 mmHg; Days of Treatment: 7	Dakin	Not available		NPWTi-d- wound treatment resulted in a decrease in the mean CFU/gram of tissue culture
Kim et al. [17] (2015)		Chronic wounds (neuropathic, ischaemic, traumatic)	142 NPWT group: 74 patients • NPWTi-d- 6-min dwell group: 34 patients • NPWTi-d- 20-min dwell: 34 patients	NPWT (C) vs. NPWTi-d- (I) (2 Subgroups I1 and I2); retrospective cohort-historical control design C: InfoV.A.C.; NP: -125 mm Hg, 7 days of treatment I1: V.A.C. VeraFlo; solution: polyhexanide + betaine; Dwell time: 6 min; NP: I1: 3.5 h; Pressure: − 125 mmHg; Days of treatment: 7 I2: V.A.C. VeraFlo; solution: polyhexanide + betaine; Dwell time: 20 min; NP: 2 h; Pressure: 125 mmHg; Days of treatment: 7	Prontosan	Not available		Patients treated with NPWTi-d- in the 6-min dwell group showed significantly lower rates of Higher percentages of wounds were closed before discharge (94% versus 62%) and had improved cultures for Gram-positive bacteria (90% versus 63%) (P 0001)
Wolvos [27] (2015)		Variety of infected or complex wounds	Pilot study of consecutive case series with seven patients	NPWTi-d- case series V.A.C. VeraFlo; solution: Microcyn, Dakin’s; Dwell time: 5–10 min; NP: 2–4 h; Pressure: 100–125 mmHg; Days of treatment: 7–54	Microcyn®, Dakin’s Solution® (quarter strength)	Six months after surgery	No complications noted	The overall length of therapy ranged from 7 to 54 days. Wounds were closed by primary, secondary, delayed primary intention, or an STSG. Six of seven patients got NPWTi-d-, and one patient had NPWT alone
Davis et al. [28] (2020)		Complex foot infections (Charcot arthropathy, collagen vascular disease, hypercoagulable state)	Randomized clinical study in 90 patients		Saline	12 weeks	No	Between patients treated with various NPWT devices or NPWT with and without irrigation, we were unable to detect any appreciable differences in clinical outcomes or adverse events
Sung et al. [29] (2020)		Complex and infected wounds (necrotizing fasciitis, Fournier’s gangrene, and gas gangrene)	Prospective study in 51 patients		0.9% Normal saline + 1% povidine iodine solution	Two individuals had partial graft failure, but after two weeks of secondary healing		All wounds were closed Though graft failure was noted in 2 cases, they healed by secondary healing by 2 weeks
Delapena et al. [30] (2020)		Necrotizing fasciitis	10	Wounds were intermittently managed with NPWTi-d- using HOCL	HOCL	Not available	No	Shorter hospital stays and improved wound care
Schreiner et al. [31] (2020)		Sternoclavicular joint infection	27 (21 men, 6 women)	Comparison of NPWT alone versus NPWTi-d- for the management of this condition	Polyhexanide	Not available	No	In patients with SCJI, the NPWTi-d-appears to be an effective therapy, resulting in a higher frequency of bacterial eradication and a shorter duration of wound care
Elhessey et al. [32] (2021)		Complex infected orthopaedic wounds	Prospective study in 20 patients	The VeraLink Cassette (KCI, San Antonio, Texas) spike allowed to connect to the system. Vacuum-assisted closure (VAC) therapy was selected for the pre-programmed therapy unit, and it was started to offer a 20-min soak/dwell time followed by 2 h of therapy at a pressure of 125 mm Hg and medium pressure intensity	Prontosan	Wound closure at 6 weeks		Wound closure was achieved in 65% of cases
Zhang et al. [33] (2021)		Necrotizing fasciitis	32	Following aggressive surgical debridement, NPWTi-d- was initiated by instilling solution with a set dwell time of 5–10 min, followed by continuous NPWT of 125 mm Hg for 3–5 h	Prontosan	After 9–16 days	No	All wounds were successfully closed and no recurrence of infection or adverse event was observed during NPWTi-d-treatment
Enodien et al. [34] (2021)		Diabetic foot syndrome		Following surgical debridement, ActiMaris sensitiveTM NPWTi-d- with super oxidised solution was infused. NaCl 1.2% and NaOCl 0.04% make up the alkaline (pH 8.5–10) hypertonic sea salt solution	Super oxidized solution	Six weeks		After 14 days of therapy, the wound and granulation tissue recovered quickly
Pellegrin et al. [35] (2023)		Chronic wounds in orthoplastic surgery	To compare outcome of NPWTi-d- vs standard of care in orthoplastic surgeries		Saline	Not available	No	The results demonstrated that infected wounds treated with NPWTi-d- had a successful outcome when compared to NPWT