Introduction

High intracranial pressure (ICP) and low cerebral per-fusion pressure (CPP) are serious threats after head in-jury [1]. ICP monitoring and control are, therefore, cru-cial in the care of severe head-injured patients. Despitethis, ICP control is still not widely used in Americanand European centers [2, 3]. Indications for ICP moni-toring are still being debated [4, 5] and complications

feared. Many aspects of ICP therapy, such as hyperven-tilation or vasopressors, are controversial [6±9]. We re-port on a series of patients managed with combined sur-gical and medical interventions aimed at controllingICP and CPP. We set out to describe the patterns ofICP and CPP, to quantify the complications of ICP mon-itoring, and to summarize a management protocol andits results.

N. StocchettiS. RossiF.BuzziC. MattioliA. PaparellaA. Colombo

Intracranial hypertension in head injury:management and results

Received: 23 June 1998Accepted: 7 January 1999

N. Stocchetti ()) × S.Rossi × A. ColomboNeuroscience ICU,Department of Anesthesia and IntensiveCare, Ospedale Maggiore,Policlinico IRCCS, Milano, Italy

F.Buzzi × A. PaparellaDepartment of Anesthesia and IntensiveCare, Ospedale di Parma, Italy

C.MattioliDepartment of Anesthesia and IntensiveCare, Ospedale S. Raffaele IRCCS,Milano, Italy

Mailing address:Neuroscience Intensive Care,Policlinico Hospital IRCCS±Milano,Via Francesco Sforza 35, 20122 Milano,Italyemail: stocchet@polic.cilea.itTel.: + 39 (2) 5503 5517,Fax: + 39 (2) 5990 2239

Abstract Objective: (1) To describethe pattern of intracranial pressure(ICP) and cerebral perfusion pres-sure (CPP) in a group of severehead-injured patients, (2) to quanti-fy complications of ICP monitoring,and (3) to describe a managementprotocol and its results.Design: Prospective observationalstudy.Setting: General intensive care unitin a teaching hospital.Patients: 138 comatose patients, se-lected according to the followingcriteria: age > 16 years, coma [Glas-gow Coma Scale (GCS) K 8] with atleast one pupil reactive after resus-citation, digital recording of intra-cranial and arterial pressure, andjugular saturation measurements.Measurements and results: MedianGCS was 5, and 62 patients had sig-nificant extracranial injuries; 71 hadintracranial hematomas, which wereurgently evacuated. Mean ICP was20.5 mm Hg (SD 8.34), mean CPPwas 71.86 mm Hg (SD 11.22); cere-bral extraction of oxygen averaged

29%. Medical therapy was used tocontrol ICP in 130 cases; 93 patientsrequired hyperventilation. Vaso-pressors were infused in 16 cases; in14 cases a barbiturate infusion wasstarted. In 6 patients all pharmaco-logical treatments failed and surgi-cal decompression was done. Theonly complication of ICP monitor-ing was meningitis in 3 patients.Outcome at 6 months was a goodrecovery and moderate disability for82 patients (59.4 %), severe disabil-ity and vegetative status for 37(26.8 %), and 19 patients died(13.7 %). The severity of intracra-nial hypertension was related topoorer results at 6 months.Conclusions: Intracranial hyperten-sion is very frequent in severe headinjury but can be reasonably wellcontrolled by combined surgical andmedical therapy.

Key words Cerebral extraction ofoxygen × Cerebral perfusionpressure × Head injury × Intracranialpressure × Outcome

Intensive Care Med (1999) 25: 371±376Ó Springer-Verlag 1999 ORIGINAL

Patients and methods

From 1 January 1990 to 31 December 1994, 715 head-injured pa-tients with a Glasgow Coma Scale (GCS) score on admission ofK 8 were admitted to the intensive care unit (ICU) of Parma Gen-eral Hospital; 420 underwent ICP monitoring. A prospective studywas carried out in 138 cases, according to the following criteria: age> 16 years; coma (GCS K 8) after resuscitation; at least one pupilreactive after resuscitation; digital recording of intracranial and ar-terial pressures; jugular venous saturation measurements.

General management

All patients were artificially ventilated to achieve an arterial oxy-gen tension of at least 100 mmHg and an arterial carbon dioxidetension (PaCO2) as required to control ICP without inducing jugu-lar desaturation. Hemodynamic monitoring included arterial pres-sure and central venous pressure in all cases; in selected cases aSwan-Ganz catheter was inserted. The hemoglobin concentrationwas kept at around 10 g/100 ml using red cell transfusions if neces-sary. The target mean arterial pressure was 80±90 mm Hg foryoung people and 90±110 mmHg for people over 60 years of age(or with a history of arterial hypertension). Central venous pres-sure was kept between 8 and 12 mmHg and/or wedge pressure be-tween 10 and 14 mmHg. Plasma sodium concentration was keptbetween 140 and 148 mEq/l.

Enteral nutrition was started early, on the day of admissionwhen possible. No patient received steroids or prophylactic anti-biotics. Sedation was maintained through an infusion of propofol(25±30 mg/kg per h) and fentanyl (0.5±1 mg/kg per h) during thefirst 2 days. For cost containment reasons, propofol was replacedby diazepam (0.04±0.21 mg/kg per h) from the third day.

Data acquisition and ICP monitoring

ICP was measured through an intracranial fluid-filled siliconcatheter. The criteria for ICP monitoring were a GCS score lessthan 9, with a motor response less than 5 and a positive computedtomographic result (CT). A CT was defined as positive in cases ofsurgical intracranial masses or compressed or absent basal cisterns.All ICP catheters were positioned in the operating room; if thefrontal horn of the lateral ventricle could not be entered after twoattempts, the catheter was inserted under the dura. Monitoringwas stopped and the catheter removed when the ICP value re-mained stable below the threshold of treatment for 24 h.

ICP and CPP data were averaged every 12 h after manual filter-ing in order to exclude artifacts. The mean ICP and CPP for every12-h interval were summarized as the ªmean average valueº. Themean during the 12-h interval in which ICP or CPP showed theworst data (higher mean ICP and lower CPP) was indicated as theªmean worst dataº. For example, if a patient had an ICP of 20, 26,and 20 mmHg during the three 12-h intervals in which his 36-h re-cording was subdivided, his ªmean average ICPº was 22 mmHgand his ªmean worst ICPº was 26 mmHg. ICP, CPP, and other phy-siological data were sent to a computer through an AD converter(MacLab, World Precision Instruments), sampled at a rate of 20 Hz.

ICP treatment

The treatment of high ICP was based on a standard regimen.Thresholds of treatment were an ICP higher than 20 mmHg inthe first 3 days, or higher than 25 mmHg later on. ICP treatment

was decided on according to the following algorithm. First, on ad-mission and in cases of a sustained increase of ICP, the presenceof a surgical mass was suspected and ruled out through CT. Anyidentified mass for which surgical removal was indicated was ur-gently operated on. Once any surgical indication was excluded,any avoidable cause of increased ICP (such as erroneous position-ing, hyponatremia, fever, etc.) was investigated and eliminated.After that, medical ICP therapy was applied in steps, as reportedin Table 1.

Jugular venous saturation

The internal jugular vein was cannulated with a Teflon catheter(Seldicath 3876.10 I Plastimed, France) on the side with the biggerjugular foramen. Samples were obtained twice a day in all cases ofhigh ICP, or when the ventilatory setting was modified. Samplescollected from the internal jugular bulb and the arterial catheterswere processed in a blood gas analyzer (Radiometer ABL 3) anda Co-Oximeter (Instrumentation Laboratory 482 Co-Oximeter).Cerebral extraction of oxygen was calculated as the difference be-tween arterial and jugular hemoglobin saturation. Lactate concen-trations in the arterial and jugular samples were checked twice aday and their difference reported.

Outcome

Outcome was assessed by phone interview 6 months after traumausing a questionnaire. Patients were grouped in a simplifiedthree-category Glasgow Outcome Score: Recovered, i. e., good re-covery and moderate disability, Not recovered, i. e., severe disabil-ity and vegetative status, and Death.

Statistical analysis

Analysis of variance was used to compare means and chi-square tocompare frequencies. A value of p < 0.05 was considered signifi-cant.

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Table 1 Steps for the management of intracranial hypertension

Step 1· Moderate sedation (fentanyl 0.5 mg/kg per h and diazepam

0.04 mg/g per h)· Moderate hyperventilation (PaCO2 35 mmHg)· Cerebrospinal fluid drainage (when ventricular catheters were

in place)· Mannitol up to 1 g/kg per day

Step 2· Deep sedation (fentanyl 1 mg/kg per h and diazepam 0.21 mg/kg

per h) and myorelaxants· Additional doses of mannitol, up to 2 g/kg per day, or until the

sodium plasma concentration does not exceed 148 mEq/l· Hyperventilation (down to a PaCO2 25 mmHg) as required to

reduce ICP without desaturation (defined as HbO2 < 55%) inthe jugular bulb

Step 3· Vasopressors (norepinephrine 4±10 mg/kg per h and dopamine

2±4 mg/kg per h)· Infusion of barbiturates and/or surgical decompression

Results

General data

We enrolled 138 patients, 108 of them males, mean age33.78 years (SD 15.71, range 16±77); GCS (best after re-suscitation) was less than 9 for all patients, and the me-dian was 5. Sixty-two patients had major extracranial in-juries, such as chest trauma or abdominal bleeding.Mean arterial pressure (MAP) was 92.39 mm Hg (SD10.31); in 13 patients MAP fell below 80 mm Hg duringtheir ICU stay. Arterial saturation of hemoglobin wasgreater than 97% in all cases; only on three occasionswere sudden decreases of saturation seen in 2 patients(due to clots in the bronchial tree) and promptly re-versed.

CT diagnosis and surgical treatment

The primary diagnosis from CT was epidural hematomain 28 patients and subdural hematoma in 38 patients;contusions were the main lesion in 54 cases and diffusedamage was diagnosed in 18 cases. The median GCSwas 6 for epidural hematomas and 5 for the other CTgroups. Basal cisterns were compressed and/or absentin 75 cases. Intracranial masses were surgically removedin the first 2 days after trauma for 73 patients; of those,28 were treated for epidural hematoma, 38 for subduralhematoma, and 7 for contusions.

ICP and CPP

ICP was measured through ventricular catheters in84 cases, and subdural catheters were used for the other54. The mean duration of ICP monitoring was 90.78 h(SD 54.03). Mean average ICP was 20.5 mm Hg (SD

8.34); only 8 cases did not experience an increase ofICP above 20 mm Hg lasting at least 5 min. The degreeof intracranial hypertension was not significantly differ-ent among the different CT diagnoses.

Mean average CPP was 71.86 mmHg (SD 11.22); in102 patients CPP fell below 60 mm Hg for more than5 min. In 89 patients this was exclusively due to intracra-nial hypertension.

Patients were divided into three groups according tothe mean worst ICP recorded. Cases with a mean worstICP below 20 mm Hg were indicated as ªmild ICPº,cases with a mean worst ICP from 20 to 30 mm Hg asªcontrollable ICPº, and the other cases, with a meanworst ICP greater than 30 mm Hg, as ªsevere ICPº.There were 47 mild ICP cases, 63 with controllable ICPand 28 in the group with the highest ICP. Main data re-garding the composition of the three groups are shownin Table 2. Basal cisterns were normal in 66 % of caseswith mild ICP, in 46% with controllable ICP, and inonly 11% of cases with very severe intracranial hyper-tension.

Cerebral extraction of oxygen and lactate

A total of 738 jugular samples were collected for cere-bral extraction of oxygen (CEO2) measurements, witha mean of five per patient. Mean CEO2 was 28.71 %(SD 7.89); 35 cases suffered at least one incrase ofCEO2 greater than 43%, and 16 cases an increase great-er than 48 % [6]. Sixty per cent of the cases with highCEO2 were detected during the first 24 h after trauma.

CEO2 did not change consistently during episodes ofraised ICP. On average, CEO2 was 23 % (SD 7.2) whenICP was greater than 40 mm Hg. Marked jugular de-saturation (CEO2 higher than 48%) occurred in only2 cases, and extraction was very low in 8 patients. A re-duction of CPP below the threshold of autoregulation

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Mild ICP Controllable ICP Severe ICP

No. of patients 47 63 28

Mean age (years) 33.76 32.2 37.2

Median GCS 6 5 4

Surgical masses[No. (%)]

17 (36) 35 (55) 14 (14)

Diffuse damage[No. (%)]

9 (19) 6 (9) 3 (11)

Basal cisterns normal[No. (%)]

31 (66) 29 (46) 3 (11)

Mean (SD) worst ICP 16.45 (3.12) 25.38 (2.7) 45.5 (15.73)

Mean (SD) worst CPP 71.02 (11.8) 61.22 (7.86) 48.28 (9.84)

Mean (SD) duration of ICP 4.83 (1.9) 8.56 (4.48) 9.75 (5.7)monitoring (days)

Table 2 Main data for thegroups with different intracra-nial pressurea

a Length of stay was calculatedfor all cases discharged alivefrom the intensive care unit

was expected to cause a reduction of cerebral bloodflow and, therefore, an increase in oxygen extraction.CPP was, in fact, below 60 mm Hg in 102 measurements,but during these episodes the mean CEO2 was 28% (SD8.09); CEO2 was higher than 48 % only in 3 cases.

There were no differences among the groups withdifferent ICPs regarding CEO2, which averaged 29%in both the mild ICP and controllable ICP groups, and26.71 % in the group with the worst ICP. More episodesof jugular desaturation were detected in the group withcontrollable ICP. The mean arterojugular difference forlactate (AJDL) was measured 271 times in 73 patientsand was 0.01 mml/l (SD 0.39); 10 patients had a negativedifference, and only 1 had an AJDL below � 0.5 mml/l.

Therapy for ICP

Only 8 patients, all belonging to the mild ICP group, re-quired no active treatment for ICP; 99 patients (72 %)had rises in ICP due at least partly to avoidable factorssuch as hyponatremia and fever. Step 1 treatment wasused in 130 cases (Table 1), and was the only step neces-sary to control ICP in 35 cases. Cerebrospinal fluid(CSF) was withdrawn in 78 patients who had ventricularcatheters in place, and low-dose mannitol was infused in118 cases.

Ninety-five patients required further therapy, and in79, step 2 was adequate to reverse the intracranial hy-pertension. Profound hyperventilation was necessaryfor 93 patients who had high jugular saturation. Thesepatients had no cerebral production of lactate and, onthe assumption that low CEO2 without evidence ofanaerobic metabolism made hyperventilation safe,PaCO2 levels as low as 25 mm Hg were achieved inter-mittently and held as long as necessary to control ICP.

No case of renal failure occurred as a result of thetherapy or of concurrent extracranial lesions.

Sixteen patients required aggressive treatment. Va-sopressors were infused in 16 cases to induce arterial hy-pertension. In 2 patients this was effective and ICP wascontrolled, and for the other 14 cases a barbiturate infu-sion was started. In 6 patients all pharmacological treat-ments failed and surgical decompression was done.

Complications of ICP monitoring

There were no hemorrhages related to insertion of theintracranial catheter. Meningitis was diagnosed in 3 pa-tients who had systemic signs of infection, with signs ofmeningeal inflammation and growth of bacteria on cul-ture. These were patients with an intraventricular can-nulation. Two of them had a concomitant CSF fistula.All recovered from the infection after appropriate anti-biotic treatment and removal of the ICP catheter.

Outcome

Outcome at 6 months showed 82 patients (59.4 %) hadrecovered, including cases with good recovery and mod-erate disability; 37 cases (26.8 %) had not recovered, in-cluding severe disability and vegetative status; and 19head-injured patients (13.7 %) had died. Nine of thesedeaths occurred during the first 4 days and 5 occurredin the next 3 days; thus 74% of deaths occurred duringthe first week. All these 14 deaths were directly due tothe brain damage. The subsequent 5 deaths were dueto brain damage in 2 cases, sepsis in 2 cases, and pul-monary embolism in 1 case.

The severity of intracranial hypertension was associ-ated with poorer results at 6 months, and the distribu-tion of outcome in the three ICP groups (Table 3)showed significant differences. ICP was not the onlyvariable related to outcome, since age and neurologicalpresentation after stabilization showed a strong associa-tion with the Glasgow Outcome Scale. Age and admis-sion GCS score were significantly related to outcome.Patients with a good recovery or moderate disabilitywere younger (mean age 29 years) than cases who re-mained severely disabled (mean age 40 years) or died(mean age 40 years) (p = 0.0002). Accordingly, the ad-mission GCS was worse for cases with a worse outcome:the median GCS was 6 for patients with a good recoveryor moderate disability, 5 for patients who remainedseverely disabled, and 4 for patients who died(p < 0.0001).

Discussion

In many centers, management of head-injured patientsis based on the assumption that strategies to controlICP are advantageous because intracranial hyperten-sion is associated with mortality and morbidity. How-

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Table 3 Outcome at 6 months in groups with different intracranialpressuresa

MildICP

ControllableICP

SevereICP

No. % No. % No. %

Recovered 28 60 44 70 10 36Not recovered 16 34 14 22 7 25Death 3 6 5 8 11 39Total 47 63 28

p = 0.0002a The table summarizes a simplified, three-category Glasgow Out-come Score: Recovered, comprising cases with good recovery andmoderate disability, Not recovered, comprising severe disabilityand vegetative status, and Death. The chi-square analysis showedsignificant differences in the distribution of outcome among thethree ICP groups

ever, this belief is not universally held, since ICP moni-toring is still not used in the majority of ICUs [2, 3, 10]and there is a great deal of controversy about what spe-cific strategy is safest and most effective [7±9].

Indications for ICP monitoring are still being de-bated. In our series, the simple combination of a GCSscore of less than 9 (with a motor response less than 5)and a positive CT identified most of the patients (130out of 138) who had an ICP higher than 20 mm Hg andrequired active treatment. Our series comprised a se-lected group of cases in whom digital recording of themain intracranial and systemic parameters allowed me-ticulous documentation of the course and treatment ofICP. Cases judged unsalvageable were excluded fromthe digital monitoring, which might partly explain thevery encouraging outcome, although it compares favor-ably with other series [9, 11].

Urgent neurosurgical operations were necessary inapproximately half the cases. While the specific lesiondetected on CT was not associated with any pattern ofintracranial hypertension, abnormal basal cisterns weresignificantly more frequent in the most severe ICPgroups. Absent or compressed basal cisterns have beenassociated with poorer outcome, and the likelihood ofintracranial hypertension in such patients is extremelyhigh [12]. Our classification of ICP severity based onthe mean worst ICP was arbitrary, but it helped identifythree specific groups.

The group with mild ICP was admitted to the ICUwith a better neurological status and 66% of these caseshad no signs of compression of the basal cisterns. ICPwas managed without particular difficulties since thecombination of therapies ± sedation, mannitol, andCSF removal ± was effective. Intracranial pressure wasback to normal within a few days, and the final outcomewas classified as ªrecoveredº in 60 % of cases.

The group with controllable ICP showed greaterneurological damage on admission and more surgicalmasses. Compression of the basal cisterns was found inhalf the cases and ICP required more than 1 week of

monitoring and treatment. More intensive therapy wasnecessary in most cases in this group, but the outcomewas still very satisfactory, since 70% of the patients re-covered.

The picture is completely different for cases with se-vere ICP, who started with a poor neurological status(median GCS score 4) and compression of the basal cis-terns in 89% of cases. ICP remained high despite treat-ment in most cases, since extreme treatments were nec-essary in 16 cases. Outcome was significantly worse inthis group, as expected.

Cerebral extraction of oxygen was used extensivelyin these patients, both to detect episodes of desaturation(observed in approximately 25% of cases, mainly dur-ing the early phases after trauma) and for guidancewhen hyperventilation was necessary. Low levels of ex-traction were more often associated with intracranialhypertension, even when CPP was below the thresholdof autoregulation. One possible explanation is that de-pression of oxygen consumption and/or relative hypere-mia [11, 13] were associated with high ICP. As cerebralblood flow was not measured, the exact mechanismleading to low CEO2 is unclear.

The rate of meningeal infections complicating ICPmonitoring was very low and probably reflected thehigh standard of care achieved in the ICU [14, 15].

In conclusion, comatose head-injured patients weretreated in the intensive care setting with a protocol basedon early evacuation of masses, physiological monitoring,and escalating therapy. Aggressive treatment was re-served for the most severe cases. Satisfactory control ofICP and CPP and a good outcome were achieved with alow level of complications related to the monitoring.This therapeutic approach would not have been possiblewithout the physiological information provided by themonitoring. Our data do not prove that the favorableoutcome in this series depends on the use of multimodal-ity monitoring, but it certainly seems unlikely that thesame level of physiological restoration would have beenpossible without measuring the therapeutic targets.

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