The British Journal of S u r g e r y Vol. 65 :No. 9 : September 1978 ~~~
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Br. J. Surg. Vol. 65 (1978) 597-600
Randomized multicentre trial of oral bowel preparation and antimicrobials for elective colorectal operations* D . M. M A T H E S O N , Y . A R A R I , D. B A X T E R - S M I T H , J . A L E X A N D E R - W I L L I A M S A N D M. R. B. K E I G H L E Y T SUMMARY
Patients and methods
A study o f 120 ptitients undergoing elective colorectal
The study was conducted at three Birmingham hospitals with eleven surgical units participating. At each hospital a liaison officer allocated patients to the different treatment groups and collected clinical information on postoperative progress. Allocation to.the type of bowel preparation (conventional or elemental diet) and the nature of prophylactic antimicrobial therapy (neomycin and metronidazole or identical placebo) was determined by drawing from a sealed envelope a card which defined the type of bowel preparation and a treatment code (tablets A or B). This treatment code was known to neither the surgical team nor the liaison officer until the end of the study. One hundred and twenty patients requiring elective operations for colorectal cancer or diverticular disease were admitted to the trial. Ten patients were subsequently excluded because of failure to complete the specified bowel preparation or owing to the need for emergency intervention to relieve obstruction or drain a pericolic abscess. Patients with ulcerative colitis and Crohn’s disease were not included in the study.
operations has investigated the effect of adding oral neomycin and metronidazole to bowel preparation in a double-blind randomized controlled trial. Comparisons have also been made between a standard mechanical preparation nnd the use of an elemental diet. The addition of neomvcin and metronidazole to bo we1 preparation significantly reduced the rate of wound sepsis ( P < O.O/), septicaemiu ( P < 0.02) and anastomotic dehisrence ( P < 0.02); anaerobic infections were abolished and there was a significant reduction in the incidence of aerobic Gram-negative infections. Elemental diets were shown to have no advantage over mechanical prepnuation. ELECTIVE colorectal operations are associated with a high incidence of postoperative sepsis (Burton, 1973). Most infections are endogenous and are caused by dissemination of intestinal contents either at the time of operation or postoperatively as a result of intestinal suture line dehiscence (Keighley, 1977). Attempts to reduce the high incidence of sepsis should be directed towards improvements in preoperative preparation and operative technique and the wider use of antimicrobials. It has been claimed that inefficient preoperative mechanical bowel preparation and negative nitrogen balance are associated with intestinal suture line dehiscence (Irvin and Goligher, 1973) and that meticulous operative technique will minimize the risks of postoperative sepsis (Hughes, 1972). Further reduction in postoperative sepsis may also be achieved by the addition of antimicrobials to bowel preparation (Washington et al., 1974) or by systemic chemoprophylaxis (Keighley et al., 1976). Elemental diets have recently been used for preoperative bowel preparation because they reduce the volume of faeces in the colon and maintain a positive nitrogen balance (Clotzer et al., 1973). Some of the clinical trials of elemental diet in bowel preparation have been inconclusive because of the small numbers of patients studied and inadequate standardization of nursing techniques (Johnson, 1974). The addition of oral neomycin and metronidazole to bowel preparation has been shown to reduce the counts per millilitre of organisms in the colon, even in the presence of stenosing carcinoma of the colon (Arabi et al., 1977). 47
Mechanical preparation and antimicrobials Conventional bowel preparation consisted of a low residue diet for 3 days before operation, five 15-g doses of oral magnesium sulphate 2 days before operation and an enema followed by two rectal washouts on the following day. The elemental diet (Vivonex standard) was used as the only form of calorie intake for 5 days before operation with a rectal washout on the day preceding operation. At operation the surgeon classified the faecal loading of the large bowel as ‘gross’ when the colon was loaded with faeces, ‘moderate’ when only a small amount of faecal fluid was encountered and ‘no residue’ when the colon was completely empty. For 2 days before operation the patients received either neomycin 1 g 8-hourly and metronidazole 200 mg 8-hourly or identical placebo tablets. The last dose of antimicrobials or placebo was received at 9 p.m. on the day before operation. Operiniue technique All anastomoses were performed in two layers (inner continous catgut and outer inverting interrupted silk) except for low anterior resections which were usually performed with a single layer of interrupted silk. The decision to use a proximal colostomy was left to the judgement of the individual surgeon. Drains, when used, were brought out through separate incisions. Primary closure of the perineum was used after
* These results were presented in part to the Surgical Research Society in July 1977. ? T h e General, Selly Oak and East Birmingham Hospitals. Birmingham. Correspondence to: M. R. B. Keighley, The General Hospital, Steelhouse Lane, Birmingham.
598
D. M. Matheson et al.
Table I: COMPARISON OF ANTIMICROBIAL AND PLACEBO GROUPS Neomycin and metronidazole Placebo ( n = 51) ( n = 59) Male 28 (54.9%) 35 (59.3%) Female 23 (45.1%) 24 (40.7%) Mean age 64.7 63.2 Operations 11 (21.5%) 12 (20.3%) Right-sided resection Left-sided resection with20 (39.2%) 33 (55.9%) out colostomy Abdominoperineal 13 (254%) 12 (20.3%) excision Other 7 (13.7%) 2 (3.01%) Trans-sphincteric 4 0 excision of villous papilloma Hartmann’s resection 2 0 Closure of colostomv 0 2
Table XI: RESULTS OF ANTIMICROBIAL BOWEL PREPARATION Neomycin and metronidazole Placebo [tz = 511 (n = 59) Faecal residue Gross Moderate No residue Wound sepsis Perineal sepsis (after abdominoperineal excision) Abscess Septicaemia Anastomotic dehiscence Wound dehiscence Death Total patients with postoperative sepsis Mean hospital stay
9 (17.6%) 17 (33.3%) 25 (49%) 9 (17.6%) 4/13 (31%)
0
-
0 0 1 2 11
-
(2%) (3.9%) (21.5%)
17.06
13 21 25 25 10/12 3 7 7 5
7 36
(22.03%) (35.59%) (42.37%) (42.3%)* (83%)
(5%) (11.9%)** (11.9%)** (8.5%) (11.9%) (61.1%)*
23.51 * * *
* P
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Br. J. Surg. Vol. 65 (1978) 597-600
Randomized multicentre trial of oral bowel preparation and antimicrobials for elective colorectal operations* D . M. M A T H E S O N , Y . A R A R I , D. B A X T E R - S M I T H , J . A L E X A N D E R - W I L L I A M S A N D M. R. B. K E I G H L E Y T SUMMARY
Patients and methods
A study o f 120 ptitients undergoing elective colorectal
The study was conducted at three Birmingham hospitals with eleven surgical units participating. At each hospital a liaison officer allocated patients to the different treatment groups and collected clinical information on postoperative progress. Allocation to.the type of bowel preparation (conventional or elemental diet) and the nature of prophylactic antimicrobial therapy (neomycin and metronidazole or identical placebo) was determined by drawing from a sealed envelope a card which defined the type of bowel preparation and a treatment code (tablets A or B). This treatment code was known to neither the surgical team nor the liaison officer until the end of the study. One hundred and twenty patients requiring elective operations for colorectal cancer or diverticular disease were admitted to the trial. Ten patients were subsequently excluded because of failure to complete the specified bowel preparation or owing to the need for emergency intervention to relieve obstruction or drain a pericolic abscess. Patients with ulcerative colitis and Crohn’s disease were not included in the study.
operations has investigated the effect of adding oral neomycin and metronidazole to bowel preparation in a double-blind randomized controlled trial. Comparisons have also been made between a standard mechanical preparation nnd the use of an elemental diet. The addition of neomvcin and metronidazole to bo we1 preparation significantly reduced the rate of wound sepsis ( P < O.O/), septicaemiu ( P < 0.02) and anastomotic dehisrence ( P < 0.02); anaerobic infections were abolished and there was a significant reduction in the incidence of aerobic Gram-negative infections. Elemental diets were shown to have no advantage over mechanical prepnuation. ELECTIVE colorectal operations are associated with a high incidence of postoperative sepsis (Burton, 1973). Most infections are endogenous and are caused by dissemination of intestinal contents either at the time of operation or postoperatively as a result of intestinal suture line dehiscence (Keighley, 1977). Attempts to reduce the high incidence of sepsis should be directed towards improvements in preoperative preparation and operative technique and the wider use of antimicrobials. It has been claimed that inefficient preoperative mechanical bowel preparation and negative nitrogen balance are associated with intestinal suture line dehiscence (Irvin and Goligher, 1973) and that meticulous operative technique will minimize the risks of postoperative sepsis (Hughes, 1972). Further reduction in postoperative sepsis may also be achieved by the addition of antimicrobials to bowel preparation (Washington et al., 1974) or by systemic chemoprophylaxis (Keighley et al., 1976). Elemental diets have recently been used for preoperative bowel preparation because they reduce the volume of faeces in the colon and maintain a positive nitrogen balance (Clotzer et al., 1973). Some of the clinical trials of elemental diet in bowel preparation have been inconclusive because of the small numbers of patients studied and inadequate standardization of nursing techniques (Johnson, 1974). The addition of oral neomycin and metronidazole to bowel preparation has been shown to reduce the counts per millilitre of organisms in the colon, even in the presence of stenosing carcinoma of the colon (Arabi et al., 1977). 47
Mechanical preparation and antimicrobials Conventional bowel preparation consisted of a low residue diet for 3 days before operation, five 15-g doses of oral magnesium sulphate 2 days before operation and an enema followed by two rectal washouts on the following day. The elemental diet (Vivonex standard) was used as the only form of calorie intake for 5 days before operation with a rectal washout on the day preceding operation. At operation the surgeon classified the faecal loading of the large bowel as ‘gross’ when the colon was loaded with faeces, ‘moderate’ when only a small amount of faecal fluid was encountered and ‘no residue’ when the colon was completely empty. For 2 days before operation the patients received either neomycin 1 g 8-hourly and metronidazole 200 mg 8-hourly or identical placebo tablets. The last dose of antimicrobials or placebo was received at 9 p.m. on the day before operation. Operiniue technique All anastomoses were performed in two layers (inner continous catgut and outer inverting interrupted silk) except for low anterior resections which were usually performed with a single layer of interrupted silk. The decision to use a proximal colostomy was left to the judgement of the individual surgeon. Drains, when used, were brought out through separate incisions. Primary closure of the perineum was used after
* These results were presented in part to the Surgical Research Society in July 1977. ? T h e General, Selly Oak and East Birmingham Hospitals. Birmingham. Correspondence to: M. R. B. Keighley, The General Hospital, Steelhouse Lane, Birmingham.
598
D. M. Matheson et al.
Table I: COMPARISON OF ANTIMICROBIAL AND PLACEBO GROUPS Neomycin and metronidazole Placebo ( n = 51) ( n = 59) Male 28 (54.9%) 35 (59.3%) Female 23 (45.1%) 24 (40.7%) Mean age 64.7 63.2 Operations 11 (21.5%) 12 (20.3%) Right-sided resection Left-sided resection with20 (39.2%) 33 (55.9%) out colostomy Abdominoperineal 13 (254%) 12 (20.3%) excision Other 7 (13.7%) 2 (3.01%) Trans-sphincteric 4 0 excision of villous papilloma Hartmann’s resection 2 0 Closure of colostomv 0 2
Table XI: RESULTS OF ANTIMICROBIAL BOWEL PREPARATION Neomycin and metronidazole Placebo [tz = 511 (n = 59) Faecal residue Gross Moderate No residue Wound sepsis Perineal sepsis (after abdominoperineal excision) Abscess Septicaemia Anastomotic dehiscence Wound dehiscence Death Total patients with postoperative sepsis Mean hospital stay
9 (17.6%) 17 (33.3%) 25 (49%) 9 (17.6%) 4/13 (31%)
0
-
0 0 1 2 11
-
(2%) (3.9%) (21.5%)
17.06
13 21 25 25 10/12 3 7 7 5
7 36
(22.03%) (35.59%) (42.37%) (42.3%)* (83%)
(5%) (11.9%)** (11.9%)** (8.5%) (11.9%) (61.1%)*
23.51 * * *
* P
