1194 of drugs for the treatment of persistent major disturbances varied considerably between indihaemodynamic viduals. Re-exploration of the abdomen (where relevant) in order to eliminate the source of continuing sepsis, was not routinely carried out. During the later stage of the study, team procedure and methods of treatment were modified on the basis of early results. i.P.P.v. was started early in the course of the illness, often in anticipation of deterioration in pulmonary gasexchange. A number of patients who had intractable respiratory disturbances were given positive end-expiratory pressure (P.E.E.P.) as well. With the benefit of hindsight it was clear that a consistent antibiotic policy was possible and a combination of gentamicin and lincomycin was used as the first choice. The main change in the drug regimen was the almost routine digitalisation of patients at the time of referral. Indications for the use of other vasoactive agents (e.g., isoprenaline and oc-adrenoreceptor-blocking agents) became more clearly defined. As a matter of policy neither steroids nor anticoagulants were administered during the course of the study although a small number of patients had received physiological doses of steroid before referral to the shock team. After resuscitation, further surgery was routinely undertaken in those patients in whom continuing sepsis was known to be present or was suspected. The clinical course of all the patients was followed throughout their stay in the I.T.u. and thereafter for a total of three
given. The
Hospital Practice PROSPECTIVE STUDY OF THE TREATMENT OF SEPTIC SHOCK I. MCA. LEDINGHAM
C. S. MCARDLE
University Department of Surgery and Intensive Therapy Unit, Western Infirmary, Glasgow G11 6NT A study of 113 patients with septic shock admitted to an intensive therapy unit (I.T.U.) during a 3-year period showed that a significant reduction in mortality was achieved after the introduction of a treatment programme which included early intermittent positive-pressure ventilation and aggressive surgery in addition to conventional management with fluids, oxygen, and antibiotics. Vasoactive drugs played an important but not essential role in therapy.
Summary
INTRODUCTION
A
RETROSPECTIVE
mortality
study
from this
centre
showed that
group of 80 patients with septic The present report is the final analysis
amongst
use
months.
a
shock was 70%.1 of the clinical and laboratory data collected during a prospective study of a similar population of patients and describes the effect of treatment on early and late survival. The preliminary results of this study have been published elsewhere.2·3I MATERIAL AND METHODS
113 patients were included in the 3-year study. The patients referred from all specialties within the Western Infirmary, Glasgow, and from a number of neighbouring hospitals. Resuscitation and subsequent investigation and treatment were carried out in a five-bed LT.u. by a multidisciplinary Shock Team4 in collaboration with the 1.T.U. staff. None of the patients was suffering from a terminal illness. The criteria for inclusion in the study were clinical evidence of shock in the form of prostration, hypotension, pallor, cold moist skin, collapsed superficial veins, mental confusion, or oliguria,5 and a positive bacteriological culture either from blood or from a major primary source of infection. In all patients, central venous pressure (c.v.p.), intra-arterial pressure, and electrocardiogram (E.C.G.) were recorded, the latter two being displayed continuously on an oscilloscope. Other measurements included hourly urine output, core/peripheral temperature gradient,6 and detailed fluid balance. Investigations also included frequent blood-gas determinations and tests for additional respiratory data in ventilated patients. Sometimes more sophisticated measurements, including cardiac output and pulmonary vascular pressures by a Swan-Ganz catheter, were made; further data were derived from these absolute measurewere
ments.
During the first year of the study, treatment was conducted along conventional lines. Intravenous fluids (in the first instance usually plasma) were given to correct deficits in circulating blood-volume, the optimum rate and quantity of fluid being judged by the response in c.v.p., urine output, and core/ peripheral temperature gradient. When laboratory results became available whole blood, electrolyte solutions, and bicarbonate were given as appropriate. Hypoxxmia was initially corrected by oxygen given by mask, but by intermittent positive-pressure ventilation (i.P.P.v.) if pulmonary gas-exchange deteriorated. No standard antibiotic policy had been formulated and a wide range of broad-spectrum antibiotics was
RESULTS
Clinical and Laboratory Data Of the 113 patients, 35, 35, and 43 presented in the first, second, and third years respectively. The mean age
of the group
was
5612 years (mean±s.E.) and there was
statistically significant difference from year to year. The male to female ratio was 1: 1.2. The gastrointestinal system, especially the large intestine, was the commonest primary source of sepsis (table i; In 79% of all patients septic shock had developed after surgery which in the majority of instances (67%) was semi-elective or emergency in nature; this pattern did not vary from year to year. All but 1 of the patients were either moderately or severely shocked ;4 this pattern also did not change .throughout the study. The mean total duration of shock was 17-2±1-3 h and the mean duration of shock before referral to the shock team was 7-2±1-1h. The total duration of shock did not alter during the study although the duration of shock before referral tended to increase as appropriate treatment was initiated by the ward staff. The majority of patients presented with the classical feano
TABLE I-SOURCE OF SEPSIS
1195 TABLE II-PRINCIPAL CLINICAL FEATURES RECORDED DURING THE WORST PHASE OF THE ILLNESS
organisms being coliforms, B. proteus, and Bacteroides sp.; Strep. pyogenase was the commonest gram-positive organism. During the study the proportion of cases with gram-negative sepsis increased with no change in the pattern oforganisms. 54% of patients in the first year had positive blood-cultures; during the third year the percentage of positive blood-cultures fell to 35% (presumably related to prior administration of antibiotics). Treatment
*Does
not
include 20’f of patients already on
LP.P. v.
of hypodynamic shock, but a small number (19%) hyperdynamic clinical pattern (i.e., hypotension, oliguria, and warm extremities). The total duration of shock in the latter group did not differ significantly from
tures
had
a
that of the series as a whole. The frequency of the principal clinical features as measured at the worst phase of their illness for all 113 patients is presented in table n. There was no statistically significant change in the prevalence of these features throughout the study. The blood-gas results from those patients for whom data while breathing air spontaneously are available (table III) revealed that hypoxaemia was equally common in all 3 years. The severity of metabolic acidosis did not vary significantly throughout the study in spite of the apparent reduction in the third
Almost all patients had both electrolyte and colloid infusions during the first 24 h of resuscitation in order to restore cardiovascular stability, replete extracellular fluid deficits, correct electrolyte disturbances, and maintain normal oncotic pressure. The colloid solutions most frequently used were freeze-dried plasma and plasmaprotein derivative. 55% of patients also required red-cell transfusion. During acute resuscitation intravenous feeding solutions were not given to any extent. Acidosis was corrected in 40% of patients. Diuretics were used increasingly during the 3 years; the frequency of mannitol infusion rose from 23% to 51% and a similar pattern was noted with the use of frusemide. Hypoxaemia was corrected in the first instance by the administration of oxygen by face mask. i.P.P.v. was used with increasing frequency and earlier as the study progressed (table IV); the duration of i.P.P.v. also increased. Of those ventilated, tracheostomy was carried out in 22%. (with a mean duration of 3 days) in the first year TABLE IV -INTERMITTENT POSITIVE PRESSURE VENTILATION
(I.P.P.V.)
year.
majority of patients in all 3 years had a normal sodium and chloride during the worst phase of their acute illness, and the bulk of the remainder were hyponatrsemic and hypochloraemic. There was no consistent pattern of change in serum-potassium. Many of the patients had a raised blood-urea (49% in excess of 13 mmol/1). Almost all patients were hypocalcsemic and hypoalbuminxmic. 55% of patients were anaemic and in 10% the haemoglobin was less than 8 g/dl. Thrombocytopenia was consistently present with a platelet count of less than 50 000/µl) in 53% of patients. Prothrombintime, partial thromboplastin-time, and fibrinogen-degradation products (>40 units/ml) were raised in 57%, and 75%, 57%, respectively, of patients. Gram-negative organisms predominated in cultures taken from the primary site of infection, the commonest The
serum
TABLE III-ARTERIAL BLOOD GASES MEASURED AT THE WORST PHASE OF THE ILLNESS AND WHILE PATIENTS BREATHED AIR
SPONTANEOUSLY
*Does not include 20‘ of patients already on
I.P.P.V.
*Started
in
and 53%
anticipation of deterioration
(with
a mean
in
pulmonary gas-exchange.
duration of 18
days)
in the third
year.
During the first year, the most commonly used antibiwere gentamicin, kanamycin, and ampicillin; resistant organisms including Bacteroides (6), Proteus (4), coliforms (4), and Streptococcus (1) were recorded in 7 patients. Thereafter gentamicin and lincomycin were used as the initial choice, other antibiotics (most frequently carbenicillin) being added later where appropriate ; resistant organisms developed in only 1 patient. During the third year systemic fungal infections developed in 3 patients, necessitating the use of amphotericin and 5-fluorocytocine in 2. Other drugs were also used in all 3 years. Digoxin was administered with increasing frequency (43% and 78?’:,)in the first and third years respectively) and earlier in the illness, but isoprenaline was used in 20% of patients in each of the 3 years. Thymoxamine was not used during the first year but was given to 34% of the third-year group. Other drugs included heparin which was given to 15‘: of third-year patients but not at all in the first 2 otics
years. Steroids were administered before referral to the shock team in 22% of patients but only in small physio-
1196
logical
doses and scattered
randomly throughout
the 3
years.
Other important treatment procedures included surgical intervention in order to eliminate the source of sepsis, and renal dialysis. 11% of first-year patients had further surgery compared with 44% of the third-year group. None of the first-year patients with renal failure survived long enough to be dialysed but 15% of the
third-year group were dialysed. Mortality Overall mortality fell from 71% for the first-year group to 54% and 47% for the second and third year patients respectively (fig. 1). The pattern of mortality also altered. In the first year of the study 76% (19/25) of deaths occurred within the first 3 days. and most were attributable to continuing shock, cardiac arrest, and acute respiratory failure in the presence of uncontrolled sepsis; 8% of the deaths occurred after 14 days (fig. 2). By the third year deaths occurring within the first 3 days fell to 25% (5/20 and only 2 from continuing shock) and 50% died at various intervals after 14 days. The causes of later deaths fell into two categories. 5 patients died in the I.T.u. from acute respiratory failure and acute renal failure in association with continuing
sepsis; the other 5 patients returned to the referring ward and died there usually as a result of cardiac arrest associated with recurring sepsis. Mortality was related to age (non-survivors 39±2 and to the nature years, survivors 53±2 years; p
given. The
Hospital Practice PROSPECTIVE STUDY OF THE TREATMENT OF SEPTIC SHOCK I. MCA. LEDINGHAM
C. S. MCARDLE
University Department of Surgery and Intensive Therapy Unit, Western Infirmary, Glasgow G11 6NT A study of 113 patients with septic shock admitted to an intensive therapy unit (I.T.U.) during a 3-year period showed that a significant reduction in mortality was achieved after the introduction of a treatment programme which included early intermittent positive-pressure ventilation and aggressive surgery in addition to conventional management with fluids, oxygen, and antibiotics. Vasoactive drugs played an important but not essential role in therapy.
Summary
INTRODUCTION
A
RETROSPECTIVE
mortality
study
from this
centre
showed that
group of 80 patients with septic The present report is the final analysis
amongst
use
months.
a
shock was 70%.1 of the clinical and laboratory data collected during a prospective study of a similar population of patients and describes the effect of treatment on early and late survival. The preliminary results of this study have been published elsewhere.2·3I MATERIAL AND METHODS
113 patients were included in the 3-year study. The patients referred from all specialties within the Western Infirmary, Glasgow, and from a number of neighbouring hospitals. Resuscitation and subsequent investigation and treatment were carried out in a five-bed LT.u. by a multidisciplinary Shock Team4 in collaboration with the 1.T.U. staff. None of the patients was suffering from a terminal illness. The criteria for inclusion in the study were clinical evidence of shock in the form of prostration, hypotension, pallor, cold moist skin, collapsed superficial veins, mental confusion, or oliguria,5 and a positive bacteriological culture either from blood or from a major primary source of infection. In all patients, central venous pressure (c.v.p.), intra-arterial pressure, and electrocardiogram (E.C.G.) were recorded, the latter two being displayed continuously on an oscilloscope. Other measurements included hourly urine output, core/peripheral temperature gradient,6 and detailed fluid balance. Investigations also included frequent blood-gas determinations and tests for additional respiratory data in ventilated patients. Sometimes more sophisticated measurements, including cardiac output and pulmonary vascular pressures by a Swan-Ganz catheter, were made; further data were derived from these absolute measurewere
ments.
During the first year of the study, treatment was conducted along conventional lines. Intravenous fluids (in the first instance usually plasma) were given to correct deficits in circulating blood-volume, the optimum rate and quantity of fluid being judged by the response in c.v.p., urine output, and core/ peripheral temperature gradient. When laboratory results became available whole blood, electrolyte solutions, and bicarbonate were given as appropriate. Hypoxxmia was initially corrected by oxygen given by mask, but by intermittent positive-pressure ventilation (i.P.P.v.) if pulmonary gas-exchange deteriorated. No standard antibiotic policy had been formulated and a wide range of broad-spectrum antibiotics was
RESULTS
Clinical and Laboratory Data Of the 113 patients, 35, 35, and 43 presented in the first, second, and third years respectively. The mean age
of the group
was
5612 years (mean±s.E.) and there was
statistically significant difference from year to year. The male to female ratio was 1: 1.2. The gastrointestinal system, especially the large intestine, was the commonest primary source of sepsis (table i; In 79% of all patients septic shock had developed after surgery which in the majority of instances (67%) was semi-elective or emergency in nature; this pattern did not vary from year to year. All but 1 of the patients were either moderately or severely shocked ;4 this pattern also did not change .throughout the study. The mean total duration of shock was 17-2±1-3 h and the mean duration of shock before referral to the shock team was 7-2±1-1h. The total duration of shock did not alter during the study although the duration of shock before referral tended to increase as appropriate treatment was initiated by the ward staff. The majority of patients presented with the classical feano
TABLE I-SOURCE OF SEPSIS
1195 TABLE II-PRINCIPAL CLINICAL FEATURES RECORDED DURING THE WORST PHASE OF THE ILLNESS
organisms being coliforms, B. proteus, and Bacteroides sp.; Strep. pyogenase was the commonest gram-positive organism. During the study the proportion of cases with gram-negative sepsis increased with no change in the pattern oforganisms. 54% of patients in the first year had positive blood-cultures; during the third year the percentage of positive blood-cultures fell to 35% (presumably related to prior administration of antibiotics). Treatment
*Does
not
include 20’f of patients already on
LP.P. v.
of hypodynamic shock, but a small number (19%) hyperdynamic clinical pattern (i.e., hypotension, oliguria, and warm extremities). The total duration of shock in the latter group did not differ significantly from
tures
had
a
that of the series as a whole. The frequency of the principal clinical features as measured at the worst phase of their illness for all 113 patients is presented in table n. There was no statistically significant change in the prevalence of these features throughout the study. The blood-gas results from those patients for whom data while breathing air spontaneously are available (table III) revealed that hypoxaemia was equally common in all 3 years. The severity of metabolic acidosis did not vary significantly throughout the study in spite of the apparent reduction in the third
Almost all patients had both electrolyte and colloid infusions during the first 24 h of resuscitation in order to restore cardiovascular stability, replete extracellular fluid deficits, correct electrolyte disturbances, and maintain normal oncotic pressure. The colloid solutions most frequently used were freeze-dried plasma and plasmaprotein derivative. 55% of patients also required red-cell transfusion. During acute resuscitation intravenous feeding solutions were not given to any extent. Acidosis was corrected in 40% of patients. Diuretics were used increasingly during the 3 years; the frequency of mannitol infusion rose from 23% to 51% and a similar pattern was noted with the use of frusemide. Hypoxaemia was corrected in the first instance by the administration of oxygen by face mask. i.P.P.v. was used with increasing frequency and earlier as the study progressed (table IV); the duration of i.P.P.v. also increased. Of those ventilated, tracheostomy was carried out in 22%. (with a mean duration of 3 days) in the first year TABLE IV -INTERMITTENT POSITIVE PRESSURE VENTILATION
(I.P.P.V.)
year.
majority of patients in all 3 years had a normal sodium and chloride during the worst phase of their acute illness, and the bulk of the remainder were hyponatrsemic and hypochloraemic. There was no consistent pattern of change in serum-potassium. Many of the patients had a raised blood-urea (49% in excess of 13 mmol/1). Almost all patients were hypocalcsemic and hypoalbuminxmic. 55% of patients were anaemic and in 10% the haemoglobin was less than 8 g/dl. Thrombocytopenia was consistently present with a platelet count of less than 50 000/µl) in 53% of patients. Prothrombintime, partial thromboplastin-time, and fibrinogen-degradation products (>40 units/ml) were raised in 57%, and 75%, 57%, respectively, of patients. Gram-negative organisms predominated in cultures taken from the primary site of infection, the commonest The
serum
TABLE III-ARTERIAL BLOOD GASES MEASURED AT THE WORST PHASE OF THE ILLNESS AND WHILE PATIENTS BREATHED AIR
SPONTANEOUSLY
*Does not include 20‘ of patients already on
I.P.P.V.
*Started
in
and 53%
anticipation of deterioration
(with
a mean
in
pulmonary gas-exchange.
duration of 18
days)
in the third
year.
During the first year, the most commonly used antibiwere gentamicin, kanamycin, and ampicillin; resistant organisms including Bacteroides (6), Proteus (4), coliforms (4), and Streptococcus (1) were recorded in 7 patients. Thereafter gentamicin and lincomycin were used as the initial choice, other antibiotics (most frequently carbenicillin) being added later where appropriate ; resistant organisms developed in only 1 patient. During the third year systemic fungal infections developed in 3 patients, necessitating the use of amphotericin and 5-fluorocytocine in 2. Other drugs were also used in all 3 years. Digoxin was administered with increasing frequency (43% and 78?’:,)in the first and third years respectively) and earlier in the illness, but isoprenaline was used in 20% of patients in each of the 3 years. Thymoxamine was not used during the first year but was given to 34% of the third-year group. Other drugs included heparin which was given to 15‘: of third-year patients but not at all in the first 2 otics
years. Steroids were administered before referral to the shock team in 22% of patients but only in small physio-
1196
logical
doses and scattered
randomly throughout
the 3
years.
Other important treatment procedures included surgical intervention in order to eliminate the source of sepsis, and renal dialysis. 11% of first-year patients had further surgery compared with 44% of the third-year group. None of the first-year patients with renal failure survived long enough to be dialysed but 15% of the
third-year group were dialysed. Mortality Overall mortality fell from 71% for the first-year group to 54% and 47% for the second and third year patients respectively (fig. 1). The pattern of mortality also altered. In the first year of the study 76% (19/25) of deaths occurred within the first 3 days. and most were attributable to continuing shock, cardiac arrest, and acute respiratory failure in the presence of uncontrolled sepsis; 8% of the deaths occurred after 14 days (fig. 2). By the third year deaths occurring within the first 3 days fell to 25% (5/20 and only 2 from continuing shock) and 50% died at various intervals after 14 days. The causes of later deaths fell into two categories. 5 patients died in the I.T.u. from acute respiratory failure and acute renal failure in association with continuing
sepsis; the other 5 patients returned to the referring ward and died there usually as a result of cardiac arrest associated with recurring sepsis. Mortality was related to age (non-survivors 39±2 and to the nature years, survivors 53±2 years; p
